Invited review: Bacterial lipopolysaccharides and innate immunity

Abstract

Bacterial lipopolysaccharides (LPS) are the major outer surface membrane components present in almost all Gram-negative bacteria and act as extremely strong stimulators of innate or natural immunity in diverse eukaryotic species ranging from insects to humans. LPS consist of a poly- or oligosaccharide region that is anchored in the outer bacterial membrane by a specific carbohydrate lipid moiety termed lipid A. The lipid A component is the primary immunostimulatory centre of LPS. With respect to immunoactivation in mammalian systems, the classical group of strongly agonistic (highly endotoxic) forms of LPS has been shown to be comprised of a rather similar set of lipid A types. In addition, several natural or derivatised lipid A structures have been identified that display comparatively low or even no immunostimulation for a given mammalian species. Some members of the latter more heterogeneous group are capable of antagonizing the effects of strongly stimulatory LPS/lipid A forms. Agonistic forms of LPS or lipid A trigger numerous physiological immunostimulatory effects in mammalian organisms, but — in higher doses — can also lead to pathological reactions such as the induction of septic shock. Cells of the myeloid lineage have been shown to be the primary cellular sensors for LPS in the mammalian immune system. During the past decade, enormous progress has been obtained in the elucidation of the central LPS/lipid A recognition and signaling system in mammalian phagocytes. According to the current model, the specific cellular recognition of agonistic LPS/lipid A is initialized by the combined extracellular actions of LPS binding protein (LBP), the membrane-bound or soluble forms of CD14 and the newly identified Toll-like receptor 4 (TLR4)*MD-2 complex, leading to the rapid activation of an intracellular signaling network that is highly homologous to the signaling systems of IL-1 and IL-18. The elucidation of structure-activity correlations in LPS and lipid A has not only contributed to a molecular understanding of both immunostimulatory and toxic septic processes, but has also re-animated the development of new pharmacological and immunostimulatory strategies for the prevention and therapy of infectious and malignant diseases.

References

Pfeiffer R. Untersuchungen über das Choleragift. Z Hygiene 1892; 11: 393—412.

Rietschel ET , Westphal O. Endotoxin: historical perspectives. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease. New York: Marcel Dekker, 1999; 1—30.

Coley WB Treatment of inoperable malignant tumors with the toxins of Erysipelas and the Bacillus prodigiosus. Am J Med Sci 1894 ; 108: 183—212.

Coley-Nauts H. , Swift WE , Coley BL The treatment of malignant tumors by bacterial toxins as developed by the late William B. Coley, MD, revised in the light of modern research. Cancer Res 1946; 6: 205—216.

Starnes CO Coley's toxins in perspective. Nature 1992 ; 357: 11—12.

Wiemann B. , Starnes CO Coley's toxins, tumor necrosis factor and cancer research: a historical perspective . Pharmacol Ther 1994; 64: 529—564.

Rietschel ET , Brade H. , Holst O. et al. Bacterial endotoxin: chemical constitution, biological recognition, host response, and immunological detoxification. Curr Top Microbiol Immunol 1996; 216: 39—81.

Holst O. , Ulmer AJ , Brade H. , Flad HD , Rietschel ET Biochemistry and cell biology of bacterial endotoxins. FEMS Immunol Med Microbiol 1996; 16: 83—104.

Kawahara K. , Seydel U. , Matsuura M. , Danbara H. , Rietschel ET , Zähringer U. Chemical structure of glycosphingolipids isolated from Sphingomonas paucimobilis . FEBS Lett 1991; 292: 107—110.

10.

Kawasaki S. , Moriguchi R. , Sekiya K. et al. The cell envelope structure of the lipopolysaccharide-lacking Gram-negative bacterium Sphingomonas paucimobilis . J Bacteriol 1994; 176: 284—290.

11.

Krziwon C. , Zähringer U. , Kawahara K. et al. Glycosphingolipids from Sphingomonas paucimobilis induce monokine production in human mononuclear cells. Infect Immun 1995; 63: 2899—2905.

12.

Kawahara K. , Moll H. , Knirel YA , Seydel U. , Zähringer U. Structural analysis of two glycosphingolipids from the lipopolysaccharide-lacking bacterium Sphingomonas capsulata. Eur J Biochem 2000; 267: 1837—1846.

13.

Nikaido H. , Vaara M. Outer membrane. In: Neidhardt FC. (ed) Escherichia coli and Salmonella typhimurium. Washington, DC: American Society for Microbiology, 1987; 7—22.

14.

Hayashi S. , Wu HC Lipoproteins in bacteria. J Bioenerg Biomembr 1990; 22: 451—471.

15.

Dmitriev BA , Ehlers S. , Rietschel ET Layered murein revisited: a fundamentally new concept of bacterial cell wall structure, biogenesis and function. Med Microbiol Immunol (Berl) 1999; 187: 173—181.

16.

Vaara M. Agents that increase the permeability of the outer membrane. Microbiol Rev 1992; 56: 395—411.

17.

Vaara M. Lipopolysaccharide and the permeability of the bacterial outer membrane. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease. New York: Marcel Dekker, 1999; 31—38.

18.

Hancock RE , Scott MG The role of antimicrobial peptides in animal defenses. Proc Natl Acad Sci USA 2000; 97: 8856—8861.

19.

Raetz CR Enzymes of lipid A biosynthesis: targets for the design of new antibiotics . Prog Clin Biol Res 1998; 397: 1—14.

20.

Rick PD , Raetz Crh. Microbial pathways of lipid A biosynthesis. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease. New York : Marcel Dekker, 1999; 283—304.

21.

Mamat U. , Seydel U. , Grimecke D. , Holst O. , Rietschel ET Lipopolysaccharides. In: Pinto BM. (ed) Carbohydrates and their Derivatives including Tannins, Cellulose, and Related Lignins. Amsterdam: Elsevier, 1999; 179—239.

22.

Steeghs L. , den Hartog R. , den Boer A. , Zomer B. , Roholl P. , van der Ley P. Meningitis bacterium is viable without endotoxin. Nature 1998; 392: 449—450.

23.

Pridmore AC , Wyllie DH , Abdillahi F. et al. A lipopolysaccharide-deficient mutant of Neisseria meningitidis elicits attenuated cytokine release by human macrophages and signals via Toll-like receptor (TLR) 2 but not via TLR4/MD2. J Infect Dis 2000; 183: 89—96.

24.

Medzhitov R. , Janeway Jr CA. Self-defense: the fruit fly style. Proc Natl Acad Sci USA 1998; 95: 429—430.

25.

Hoffmann JA , Kafatos FC , Janeway Jr CA, Ezekowitz RA. Phylogenetic perspectives in innate immunity . Science 1999; 284: 1313—1318.

26.

Medzhitov R. , Janeway Jr CA. Innate immune recognition: mechanisms and pathways. Immunol Rev 2000; 173: 89—97.

27.

Medzhitov R. , Janeway Jr CA. Innate immunity. N Engl J Med 2000; 343: 338—344.

28.

Kopp EB , Medzhitov R. The Toll-receptor family and control of innate immunity. Curr Opin Immunol 1999; 11: 13—18.

29.

Qureshi ST , Gros P. , Malo D. Host resistance to infection: genetic control of lipopolysaccharide responsiveness by TOLL-like receptor genes. Trends Genet 1999; 15: 291—294.

30.

Anderson KV Toll signaling pathways in the innate immune response. Curr Opin Immunol 2000; 12: 13—19.

31.

Beutler B. Tlr4: central component of the sole mammalian LPS sensor. Curr Opin Immunol 2000; 12: 20—26.

32.

Beutler B. , Poltorak A. Positional cloning of LPS, and the general role of Toll-like receptors in the innate immune response. Eur Cytokine Netw 2000; 11: 143—152.

33.

Aderem A. , Ulevitch RJ Toll-like receptors in the induction of the innate immune response. Nature 2000; 406: 782—787.

34.

Engström Y. Induction and regulation of antimicrobial peptides in Drosophila. Dev Comp Immunol 1999; 23: 345—358.

35.

Imler JL , Hoffmann JA Signaling mechanisms in the antimicrobial host defense of Drosophila. Curr Opin Microbiol 2000; 3: 16—22.

36.

Wasserman SA Toll signaling: the enigma variations. Curr Opin Genet Dev 2000; 10: 497—502.

37.

Brightbill HD , Modlin RL Toll-like receptors: molecular mechanisms of the mammalian immune response. Immunology 2000; 101: 1—10.

38.

Glauser MP , Zanetti G. , Baumgartner JD , Cohen J. Septic shock: pathogenesis. Lancet 1991; 338: 732—736.

39.

Woltmann A. , Hamann L. , Ulmer AJ , Gerdes J. , Bruch HP , Rietschel ET

Molecular mechanisms of sepsis. Langenbecks

Arch Surg 1998; 383: 2—10.

40.

Brun-Buisson C. The epidemiology of the systemic inflammatory response. Intensive Care Med 2000; 26 (Suppl 1): S64—S74.

41.

Hurley J. , Levin J. The relevance of endotoxin detection in sepsis. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease. New York : Marcel Dekker, 1999; 841—854.

42.

Westphal O. , Lüderitz O. , Bister F. Über die Extraktion von Bakterien mit Phenol/Wasser . Z Naturforsch 1952; B 7: 148—155.

43.

Reske K. , Jann K. The O8 antigen of Escherichia coli. Structure of the polysaccharide chain . Eur J Biochem 1972 ; 31: 320—328.

44.

Prehm P. , Jann B. , Jann K. The O9 antigen of Escherichia coli. Structure of the polysaccharide chain . Eur J Biochem 1976; 67: 53—56.

45.

Curvall M. , Lindberg B. , Lonngren J. , Nimmich W. Structural studies on the Klebsiella O group 3 lipopolysaccharide. Acta Chem Scand 1973; 27: 2645—2649.

46.

Lindberg B. , Lonngren J. , Nimmich W. Structural studies on Klebsiella O group 5 lipopolysaccharides. Acta Chem Scand 1972; 26: 2231—2236.

47.

Jann K. , Jann B. Polysaccharide antigens of Escherichia coli. Rev Infect Dis 1987; 9 (Suppl 5): S517—S526.

48.

Knirel YA , Rietschel ET , Marre R. , Zähringer U. The structure of the O-specific chain of Legionella pneumophila serogroup 1 lipopolysaccharide. Eur J Biochem 1994; 221: 239—245.

49.

Zähringer U. , Knirel YA , Lindner B. et al. The lipopolysaccharide of Legionella pneumophila serogroup 1 (strain Philadelphia 1): chemical structure and biological significance. Prog Clin Biol Res 1995; 392: 113—139.

50.

Kido N. , Ohta M. , Ito H. et al. Potent adjuvant action of lipopolysaccharides possessing the O-specific polysaccharide moieties consisting of mannans in antibody response against protein antigen. Cell Immunol 1985; 91: 52—59.

51.

Kato N. , Kido N. , Ohta M. , Naito S. Comparative studies on adjuvanticity of Klebsiella O3 lipopolysaccharide and its lipid A and polysaccharide fractions. Immunology 1985; 54: 317—324.

52.

Ohta M. , Kido N. , Hasegawa T. et al. Contribution of the mannan O side-chains to the adjuvant action of lipopolysaccharides. Immunology 1987; 60: 503—507.

53.

Engering AJ , Cella M. , Fluitsma DM , Hoefsmit EC , Lanzavecchia A. , Pieters J. Mannose receptor mediated antigen uptake and presentation in human dendritic cells. Adv Exp Med Biol 1997; 417: 183—187.

54.

Tan MC , Mommaas AM , Drijfhout JW et al. Mannose receptor mediated uptake of antigens strongly enhances HLA-class II restricted antigen presentation by cultured dendritic cells. Adv Exp Med Biol 1997; 417: 171—174.

55.

Stahl PD , Ezekowitz RA The mannose receptor is a pattern recognition receptor involved in host defense . Curr Opin Immunol 1998; 10: 50—55.

56.

Schneider H. , Hale TL , Zollinger WD , Seid Jr RC , Hammack CA , Griffiss JM Heterogeneity of molecular size and antigenic expression within lipooligosaccharides of individual strains of Neisseria gonorrhoeae and Neisseria meningitidis. Infect Immun 1984; 45: 544—549.

57.

Griffiss JM , O'Brien JP , Yamasaki R. , Williams GD , Rice PA , Schneider H. Physical heterogeneity of neisserial lipooligosaccharides reflects oligosaccharides that differ in apparent molecular weight, chemical composition, and antigenic expression. Infect Immun 1987; 55: 1792—1800.

58.

Pavliak V. , Brisson JR , Michon F. , Uhrin D. , Jennings HJ Structure of the sialylated L3 lipopolysaccharide of Neisseria meningitidis . J Biol Chem 1993; 268: 14146—14152.

59.

Kogan G. Uhrin D. Brisson JR Jennings HJ Structural basis of the Neisseria meningitidis immunotypes including the L4 and L7 immunotypes. Carbohydr Res 1997; 298: 191—199.

60.

Schneider H. , Griffiss JM , Williams GD , Pier GB Immunological basis of serum resistance of Neisseria gonorrhoeae. J Gen Microbiol 1982 ; 128 : 13—22.

61.

Yamasaki R. , Kerwood DE , Schneider H. , Quinn KP , Griffiss JM , Mandrell RE The structure of lipooligosaccharide produced by Neisseria gonorrhoeae, strain 15253, isolated from a patient with disseminated infection. Evidence for a new glycosylation pathway of the gonococcal lipooligosaccharide. J Biol Chem 1994; 269: 30345—30351.

62.

Inzana TJ , Seifert Jr WE , Williams RP Composition and antigenic activity of the oligosaccharide moiety of Haemophilus influenzae type b lipooligosaccharide. Infect Immun 1985; 48: 324—330.

63.

Phillips NJ , Apicella MA , Griffiss JM , Gibson BW Structural studies of the lipooligosaccharides from Haemophilus influenzae type b strain A2. Biochemistry 1993; 32: 2003—2012.

64.

Risberg A. , Masoud H. , Martin A. , Richards JC , Moxon ER Schweda EK Structural analysis of the lipopolysaccharide oligosaccharide epitopes expressed by a capsule-deficient strain of Haemophilus influenzae Rd. Eur J Biochem 1999; 261: 171—180.

65.

Risberg A. , Schweda EK , Jansson PE Structural studies of the cell-envelope oligosaccharide from the lipopolysaccharide of Haemophilus influenzae strain RM.118-128. Eur J Biochem 1997; 243: 701—707.

66.

Peppler MS Two physically and serologically distinct lipopolysaccharide profiles in strains of Bordetella pertussis and their phenotype variants. Infect Immun 1984; 43: 224—232.

67.

Caroff M. , Brisson J. , Martin A. , Karibian D. Structure of the Bordetella pertussis 1414 endotoxin. FEBS Lett 2000; 477: 8—14.

68.

Nurminen M. , Leinonen M. , Saikku P. , Makela PH The genus-specific antigen of Chlamydia: resemblance to the lipopolysaccharide of enteric bacteria. Science 1983; 220: 1279—1281.

69.

Nurminen M. , Rietschel ET , Brade H. Chemical characterization of Chlamydia trachomatis lipopolysaccharide. Infect Immun 1985; 48: 573—575.

70.

Rund S. , Lindner B. , Brade H. , Holst O. Structural analysis of the lipopolysaccharide from Chlamydia trachomatis serotype L2. J Biol Chem 1999; 274: 16819—16824.

71.

Griffiss JM , Schneider H. , Mandrell RE et al. Lipooligosaccharides: the principal glycolipids of the neisserial outer membrane. Rev Infect Dis 1988; 10 (Suppl 2): S287—S295.

72.

Preston A. , Mandrell RE , Gibson BW , Apicella MA The lipooligosaccharides of pathogenic gram-negative bacteria. Crit Rev Microbiol 1996; 22: 139—180.

73.

Moran AP , Prendergast MM , Appelmelk BJ Molecular mimicry of host structures by bacterial lipopolysaccharides and its contribution to disease. FEMS Immunol Med Microbiol 1996; 16: 105—115.

74.

Estabrook MM , Griffiss JM , Jarvis GA Sialylation of Neisseria meningitidis lipooligosaccharide inhibits serum bactericidal activity by masking lacto-N-neotetraose. Infect Immun 1997; 65: 4436—4444.

75.

Smith H. , Cole JA , Parsons NJ The sialylation of gonococcal lipopolysaccharide by host factors: a major impact on pathogenicity. FEMS Microbiol Lett 1992; 79: 287—292.

76.

Verheul AF , Snippe H. , Poolman JT Meningococcal lipopolysaccharides: virulence factor and potential vaccine component. Microbiol Rev 1993; 57: 34—49.

77.

Jarvis GA Recognition and control of neisserial infection by antibody and complement . Trends Microbiol 1995; 3: 198—201.

78.

Clementz T. , Raetz CR A gene coding for 3-deoxy-D-mannooctulosonic-acid transferase in Escherichia coli. Identification, mapping, cloning, and sequencing . J Biol Chem 1991; 266: 9687—9696.

79.

Belunis CJ , Clementz T. , Carty SM , Raetz CR Inhibition of lipopolysaccharide biosynthesis and cell growth following inactivation of the kdtA gene in Escherichia coli. J Biol Chem 1995; 270: 27646—27652.

80.

Wyckoff TJ , Raetz CR , Jackman JE Antibacterial and anti-inflammatory agents that target endotoxin. Trends Microbiol 1998; 6: 154—159.

81.

Droge W. , Lehmann V. , Lüderitz O. , Westphal O. Structural investigations on the 2-keto-3-deoxyoctonate region of lipopolysaccharides . Eur J Biochem 1970; 14: 175—184.

82.

Brade H. , Galanos C. Common lipopolysaccharide specificity: new type of antigen residing in the inner core region of S- and R-form lipopolysaccharides from different families of Gram-negative bacteria. Infect Immun 1983 ; 42: 250—256.

83.

Westphal O. , Lüderitz O. Chemische Erforschung von Lipopolysacchariden Gram-negativer Bakterien. Angew Chemie 1954 ; 66: 407—417.

84.

Lüderitz O. , Galanos C. , Risse HJ et al. Structural relationships of Salmonella O and R antigens. Ann NY Acad Sci 1966; 133: 349—347.

85.

Kim YB , Watson DW Biologically active endotoxins from Salmonella mutants deficient in O- and R-polysaccharides and heptose. J Bacteriol 1967; 94: 1320—1326.

86.

Kasai N. , Nowotny A. Endotoxic glycolipid from a heptoseless mutant of Salmonella minnesota. J Bacteriol 1967; 94: 1824—1836.

87.

Galanos C. Physical state and biological activity of lipopolysaccharides. Toxicity and immunogenicity of the lipid A component. Z Immunol Forsch 1975; 149: 214.

88.

Imoto M. , Shiba T. , Naoki H. et al. Chemical structure of E. coli lipid A: a linkage site of acyl groups in the disaccharide backbone. Tetrahadron Lett 1983; 24: 4017—4020.

89.

Takayama K. , Qureshi N. , Mascagni P. Complete structure of lipid A obtained from the lipopolysaccharides of the heptoseless mutant of Salmonella typhimurium . J Biol Chem 1983; 258: 12801—12803.

90.

Imoto M. , Yoshimura H. , Kusumoto S. , Shiba T. Total synthesis of lipid A, active principle of bacterial endotoxin. Proc Jpn Acad Sci 1984; 60: 285—288.

91.

Galanos C. , Lüderitz O. , Rietschel ET et al. Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities. Eur J Biochem 1985; 148: 1—5.

92.

Galanos C. , Lehmann V. , Lüderitz O. et al. Endotoxic properties of chemically synthesized lipid A part structures. Comparison of synthetic lipid A precursor and synthetic analogues with biosynthetic lipid A precursor and free lipid A. Eur J Biochem 1984; 140: 221—227.

93.

Tanamoto K. , Zähringer U. , McKenzie GR et al. Biological activities of synthetic lipid A analogs: pyrogenicity, lethal toxicity, anticomplement activity, and induction of gelation of Limulus amoebocyte lysate. Infect Immun 1984; 44: 421—426.

94.

Kotani S. , Takada H. , Tsujimoto M. et al. Synthetic lipid A with endotoxic and related biological activities comparable to those of a natural lipid A from an Escherichia coli Re-mutant Infect Immun 1985; 49: 225—237.

95.

Zähringer U. , Lindner B. , Rietschel ET Chemical structure of lipid A: recent advances in structural analysis of biologically active molecule. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease. New York: Marcel Dekker , 1999; 93—114.

96.

Bhat UR , Forsberg LS , Carlson RW Structure of lipid A component of Rhizobium leguminosarum by phaseoli lipopolysaccharide. Unique nonphosphorylated lipid A containing 2-amino-2-deoxygluconate, galacturonate, and glucosamine. J Biol Chem 1994; 269: 14402—14410.

97.

Martin E. , Ganz T. , Lehrer RI Defensins and other endogenous peptide antibiotics of vertebrates. J Leukoc Biol 1995; 58: 128—136.

98.

Elsbach P. , Weiss J. Bactericidal/permeability increasing protein and host defense against Gram-negative bacteria and endotoxin. Curr Opin Immunol 1993; 5: 103—107.

99.

Peterson AA , Fesik SW , McGroarty EJ Decreased binding of antibiotics to lipopolysaccharides from polymyxin-resistant strains of Escherichia coli and Salmonella typhimurium . Antimicrob Agents Chemother 1987; 31: 230—237.

100.

Helander IM , Kilpelainen I. , Vaara M. Increased substitution of phosphate groups in lipopolysaccharides and lipid A of the polymyxin-resistant pmrA mutants of Salmonella typhimurium: a 31P-NMR study. Mol Microbiol 1994; 11: 481—487.

101.

Nummila K. , Kilpelainen I. , Zähringer U. , Vaara M. , Helander IM Lipopolysaccharides of polymyxin B-resistant mutants of Escherichia coli are extensively substituted by 2-aminoethyl pyrophosphate and contain aminoarabinose in lipid A. Mol Microbiol 1995; 16: 271—278.

102.

Helander IM , Kato Y. , Kilpelainen I. et al. Characterization of lipopolysaccharides of polymyxin-resistant and polymyxin-sensitive Klebsiella pneumoniae O3. Eur J Biochem 1996; 237: 272—278.

103.

Roland KL , Martin LE , Esther CR , Spitznagel JK Spontaneous pmrA mutants of Salmonella typhimurium LT2 define a new two-component regulatory system with a possible role in virulence. J Bacteriol 1993; 175: 4154—4164.

104.

Gunn JS , Miller SI PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance . J Bacteriol 1996; 178: 6857—6864.

105.

Guo L. , Lim KB , Gunn JS , Bainbridge B. et al. Regulation of lipid A modifications by Salmonella typhimurium virulence genes phoP-phoQ. Science 1997; 276: 250—253.

106.

Ernst RK , Yi EC , Guo L. et al. Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa. Science 1999; 286: 1561—1565.

107.

Helander IM , Lindner B. , Brade H. et al. Chemical structure of the lipopolysaccharide of Haemophilus influenzae strain I-69 Rd—/b+. Description of a novel deep-rough chemotype. Eur J Biochem 1988; 177:483—492.

108.

Loppnow H. , Brade L. , Brade H. et al. Induction of human interleukin 1 by bacterial and synthetic lipid A. Eur J Immunol 1986; 16: 1263—1267.

109.

Loppnow H. , Brade H. , Dürrbaum I. et al. IL-1 induction-capacity of defined lipopolysaccharide partial structures. J Immunol 1989; 142: 3229—3238.

110.

Feist W. , Ulmer AJ , Musehold J. , Brade H. , Kusumoto S. , Flad HD Induction of tumor necrosis factor-alpha release by lipopolysaccharide and defined lipopolysaccharide partial structures. Immunobiology 1989; 179: 293—307.

111.

Wang MH , Feist W. , Herzbeck H. et al. Suppressive effect of lipid A partial structures on lipopolysaccharide or lipid A-induced release of interleukin 1 by human monocytes. FEMS Microbiol Immunol 1990; 2: 179—185.

112.

Wang MH , Flad HD , Feist W. et al. Inhibition of endotoxin-induced interleukin-6 production by synthetic lipid A partial structures in human peripheral blood mononuclear cells. Infect Immun 1991; 59: 4655—4664.

113.

Wang MH , Flad HD , Feist W. et al. Inhibition of endotoxin or lipid A-induced tumor necrosis factor production by synthetic lipid A partial structures in human peripheral blood mononuclear cells. Lymphokine Cytokine Res 1992; 11: 23—31.

114.

Munford RS , Hall CL Detoxification of bacterial lipopolysaccharides (endotoxins) by a human neutrophil enzyme. Science 1986; 234: 203—205.

115.

Nogare AR , Yarbrough Jr WC. A comparison of the effects of intact and deacylated lipopolysaccharide on human polymorphonuclear leukocytes. J Immunol 1990; 144: 1404—1410.

116.

Somerville Jr JE , Cassiano L. , Bainbridge B. , Cunningham MD , Darveau RP A novel Escherichia coli lipid A mutant that produces an anti-inflammatory lipopolysaccharide. J Clin Invest 1996; 97: 359—365.

117.

Seydel U. , Lindner B. , Wollenweber HW , Rietschel ET Structural studies on the lipid A component of enterobacterial lipopolysaccharides by laser desorption mass spectrometry. Location of acyl groups at the lipid A backbone. Eur J Biochem 1984; 145: 505—509.

118.

Qureshi N. , Mascagni P. , Ribi E. , Takayama K. Monophosphoryl lipid A obtained from lipopolysaccharides of Salmonella minnesota R595. Purification of the dimethyl derivative by high performance liquid chromatography and complete structural determination. J Biol Chem 1985; 260: 5271—5278.

119.

Galanos C. , Lüderitz O. , Freudenberg M. et al. Biological activity of synthetic heptaacyl lipid A representing a component of Salmonella minnesota R595 lipid A. Eur J Biochem 1986; 160: 55—59.

120.

Ingalls RR , Rice PA , Qureshi N. , Takayama K. , Lin JS , Golenbock DT The inflammatory cytokine response to Chlamydia trachomatis infection is endotoxin mediated. Infect Immun 1995; 63: 3125—3130.

121.

Denlinger LC , Garis KA , Sommer JA , Guadarrama AG , Proctor RA , Bertics PJ Nuclear translocation of NF-kappaB in lipopolysaccharide-treated macrophages fails to correspond to endotoxicity: evidence suggesting a requirement for a gamma interferon-like signal. Infect Immun 1998; 66: 1638—1647.

122.

Gangloff SC , Hijiya N. , Haziot A. , Goyert SM Lipopolysaccharide structure influences the macrophage response via CD14-independent and CD14-dependent pathways. Clin Infect Dis 1999; 28: 491—496.

123.

Kulshin VA , Zähringer U. , Lindner B. et al. Structural characterization of the lipid A component of pathogenic Neisseria meningitidis. J Bacteriol 1992; 174: 1793—1800.

124.

Iwanaga S. , Kawabata S. Evolution and phylogeny of defense molecules associated with innate immunity in horseshoe crab. Front Biosci 1998; 3: D973—D984.

125.

Brandenburg K. , Mayer H. , Koch MH et al. Influence of the supramolecular structure of free lipid A on its biological activity. Eur J Biochem 1993; 218: 555—563.

126.

Seydel U. , Labischinski H. , Kastowsky M. , Brandenburg K. Phase behavior, supramolecular structure, and molecular conformation of lipopolysaccharide . Immunobiology 1993; 187: 191—211.

127.

Brandenburg K. , Seydel U. , Schromm AB , Loppnow H. , Koch Mhj , Rietschel ET Conformation of lipid A, the endotoxic center of bacterial lipopolysaccharides. J Endotoxin Res 1996; 3: 173—178.

128.

Seydel U. , Oikawa M. , Fukase K. , Kusumoto S. , Brandenburg K. Intrinsic conformation of lipid A is responsible for agonistic and antagonistic activity. Eur J Biochem 2000; 267: 3032—3039.

129.

Ferguson AD , Hofmann E. , Coulton JW , Diederichs K. , Welte W. Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide. Science 1998; 282: 2215—2220.

130.

Ferguson AD , Welte W. , Hofmann E. et al. A conserved structural motif for lipopolysaccharide recognition by procaryotic and eucaryotic proteins. Structure 2000; 8: 585—592.

131.

Qureshi N. , Kaltashov I. , Walker K. et al. Structure of the monophosphoryl lipid A moiety obtained from the lipopolysaccharide of Chlamydia trachomatis. J Biol Chem 1997; 272: 10594—10600.

132.

Salimath PV , Weckesser J. , Strittmatter W. , Mayer H. Structural studies on the non-toxic lipid A from Rhodopseudomonas sphaeroides ATCC 17023. Eur J Biochem 1983; 136: 195—200.

133.

Strittmatter W. , Weckesser J. , Salimath PV , Galanos C. Non-toxic lipopolysaccharide from Rhodopseudomonas sphaeroides ATCC 17023. J Bacteriol 1983; 155: 153—158.

134.

Krauss JH , Seydel U. , Weckesser J. , Mayer H. Structural analysis of the nontoxic lipid A of Rhodobacter capsulatus 37b4 . Eur J Biochem 1989; 180: 519—526.

135.

Loppnow H. , Libby P. , Freudenberg M. , Krauss JH , Weckesser J. , Mayer H. Cytokine induction by lipopolysaccharide (LPS) corresponds to lethal toxicity and is inhibited by non-toxic Rhodobacter capsulatus LPS. Infect Immun 1990; 58: 3743—3750.

136.

Plötz BM , Lindner B. , Stetter KO , Holst O. Characterization of a novel lipid A containing D-galacturonic acid that replaces phosphate residues. The structure of the lipid A of the lipopolysaccharide from the hyperthermophilic bacterium Aquifex pyrophilus. J Biol Chem 2000; 275: 11222—11228.

137.

Plötz BM, Ulmer AJ, Stetter KO, Holst O. Unpublished.

138.

139.

Neumeister B. , Faigle M. , Sommer M. et al. Low endotoxic potential of Legionella pneumophila lipopolysaccharide due to failure of interaction with the monocyte lipopolysaccharide receptor CD14. Infect Immun 1998; 66: 4151—4157.

140.

Golenbock DT , Hampton RY , Qureshi N. , Takayama K. , Raetz CR Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. J Biol Chem 1991; 266: 19490—19498.

141.

Lynn WA , Golenbock DT Lipopolysaccharide antagonists. Immunol Today 1992; 13: 271—276.

142.

Qureshi N. , Jarvis BW , Takayama K. Non-toxic RsDPLA as a potent antagonist of toxic lipopolysaccharide. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease. New York: Marcel Dekker, 1999; 687—698.

143.

Rossignol DP , Hawkins LD , Christ WJ et al. Synthetic endotoxin antagonists. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease. New York : Marcel Dekker, 1999; 699—717.

144.

Kitchens RL , Ulevitch RJ , Munford RS Lipopolysaccharide (LPS) partial structures inhibit responses to LPS in a human macrophage cell line without inhibiting LPS uptake by a CD14-mediated pathway. J Exp Med 1992; 176: 485—494.

145.

Flad HD , Loppnow H. , Rietschel ET , Ulmer AJ Agonists and antagonists for lipopolysaccharide-induced cytokines. Immunobiology 1993; 187: 303—316.

146.

Khan SA , Everest P. , Servos S. et al. A lethal role for lipid A in Salmonella infections. Mol Microbiol 1998; 29: 571—579.

147.

Qureshi N. , Takayama K. , Meyer KC et al. Chemical reduction of 3-oxo and unsaturated groups in fatty acids of diphosphoryl lipid A from the lipopolysaccharide of Rhodopseudomonas sphaeroides. Comparison of biological properties before and after reduction . J Biol Chem 1991; 266: 6532—6538.

148.

Christ WJ , Asano O. , Robidoux AL et al. E5531, a pure endotoxin antagonist of high potency. Science 1995; 268: 80—83.

149.

Kobayashi S. , Kawata T. , Kimura A. et al. Suppression of murine endotoxin response by E5531, a novel synthetic lipid A antagonist. Antimicrob Agents Chemother 1998; 42: 2824—2829.

150.

Kanegasaki S. , Kojima Y. , Matsuura M. et al. Biological activities of analogues of lipid A based chemically on the revised structural model. Comparison of mediator-inducing, immunomodulating and endotoxic activities. Eur J Biochem 1984; 143: 237—242.

151.

Delude RL , Savedra Jr R. , Zhao H. et al. CD14 enhances cellular responses to endotoxin without imparting ligand-specific recognition. Proc Natl Acad Sci USA 1995; 92: 9288—9292.

152.

Tanamoto K. Chemically detoxified lipid A precursor derivatives antagonize the TNF-alpha-inducing action of LPS in both murine macrophages and a human macrophage cell line. J Immunol 1995; 155: 5391—5396.

153.

Takayama K. , Qureshi N. , Beutler B. , Kirkland TN Diphosphoryl lipid A from Rhodopseudomonas sphaeroides ATCC 17023 blocks induction of cachectin in macrophages by lipopolysaccharide . Infect Immun 1989; 57: 1336—1338.

154.

Qureshi N. , Takayama K. , Kurtz R. Diphosphoryl lipid A obtained from the non-toxic lipopolysaccharide of Rhodopseudomonas sphaeroides is an endotoxin antagonist in mice. Infect Immun 1991; 59: 441—444.

155.

Kirkland TN , Qureshi N. , Takayama K. Diphosphoryl lipid A derived from lipopolysaccharide (LPS) of Rhodopseudomonas sphaeroides inhibits activation of 70Z/3 cells by LPS. Infect Immun 1991; 59: 131—136.

156.

Henricson BE , Perera PY , Qureshi N. , Takayama K. , Vogel SN Rhodopseudomonas sphaeroides lipid A derivatives block in vitro induction of tumor necrosis factor and endotoxin tolerance by smooth lipopolysaccharide and monophosphoryl lipid A. Infect Immun 1992; 60: 4285—4290.

157.

Poltorak A. , Ricciardi-Castagnoli P. , Citterio S. , Beutler B. Physical contact between lipopolysaccharide and Toll-like receptor 4 revealed by genetic complementation . Proc Natl Acad Sci USA 2000; 97: 2163—2167.

158.

Lien E. , Means TK , Heine H. et al. Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J Clin Invest 2000; 105: 497—504.

159.

Haziot A. , Chen S. , Ferrero E. , Low MG , Silber R. , Goyert SM The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. J Immunol 1988; 141: 547—552.

160.

Kitchens RL Role of CD14 in cellular recognition of bacterial lipopolysaccharides. Chem Immunol 2000; 74: 61—82.

161.

Zhang FX , Kirschning CJ , Mancinelli R. et al. Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. J Biol Chem 1999; 274: 7611—7614.

162.

Muzio M. , Bosisio D. , Polentarutti N. et al. Differential expression and regulation of Toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells . J Immunol 2000; 164: 5998—6004.

163.

Muzio M. , Polentarutti N. , Bosisio D. , Prahladan MK , Mantovani A. Toll-like receptors: a growing family of immune receptors that are differentially expressed and regulated by different leukocytes. J Leukoc Biol 2000; 67: 450—456.

164.

Verhasselt V. , Buelens C. , Willems F. et al. Bacterial lipopolysaccharide stimulates the production of cytokines and the expression of co-stimulatory molecules by human peripheral blood dendritic cells: evidence for a soluble CD14-dependent pathway. J Immunol 1997; 158: 2919—2925.

165.

Cella M. , Engering A. , Pinet V. , Pieters J. , Lanzavecchia A. Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature 1997; 388: 782—787.

166.

Banchereau J. , Steinman RM Dendritic cells and the control of immunity . Nature 1998; 392: 245—252.

167.

Reis e Sousa C. , Sher A. , Kaye P. The role of dendritic cells in the induction and regulation of immunity to microbial infection. Curr Opin Immunol 1999; 11: 392—399.

168.

Galanos C. , Rietschel ET , Lüderitz O. , Westphal O. Interaction of lipopolysaccharides and lipid A with complement. Eur J Biochem 1971; 19: 143—152.

169.

Freudenberg MA , Galanos C. Interaction of lipopolysaccharides and lipid A with complement in rats and its relation to endotoxicity. Infect Immun 1978; 19: 875—882.

170.

Cooper NR , Morrison DC Binding and activation of the first component of human complement by the lipid A region of lipopolysaccharides. J Immunol 1978; 120: 1862—1868.

171.

Vukajlovich SW Antibody-independent activation of the classical pathway of human serum complement by lipid A is restricted to Re-chemotype lipopolysaccharide and purified lipid A. Infect Immun 1986; 53: 480—485.

172.

Levin J. The horseshoe crab: a model for Gram-negative sepsis in marine organisms and humans. Prog Clin Biol Res 1988; 272: 3—15.

173.

Iwanaga S. , Miyata B. , Tokunaga F. , Muta T. Molecular mechanism of hemolymph clotting system in Limulus. Thromb Res 1992; 68: 1—32.

174.

Muta T. , Iwanaga S. Clotting and immune defense in Limulidae. Prog Mol Subcell Biol 1996; 15: 154—189.

175.

Levin J. , Bang FB The role of endotoxin in the extracellular coagulation of Limulus blood. Bull Johns Hopkins Hospital 1964; 115: 265—274.

176.

Hurley JC Endotoxemia: methods of detection and clinical correlates. Clin Microbiol Rev 1995; 8: 268—292.

177.

LeMosy EK , Hong CC , Hashimoto C. Signal transduction by a protease cascade. Trends Cell Biol 1999; 9: 102—107.

178.

Inamori K-I. , Mishima C. , Muta T. , Kawabata S-I. A horseshoe crab receptor structurally related to Drosophila Toll. J Endotoxin Res 2000; 6: 77.

179.

Takayama K. , Mitchell DH , Din ZZ , Mukerjee P. , Li C. , Coleman DL Monomeric Re lipopolysaccharide from Escherichia coli is more active than the aggregated form in the Limulus amebocyte lysate assay and in inducing Egr-1 mRNA in murine peritoneal macrophages. J Biol Chem 1994; 269: 2241—2244.

180.

Tan NS , Ho B. , Ding JL High-affinity LPS binding domain(s) in recombinant factor C of a horseshoe crab neutralizes LPS-induced lethality. FASEB J 2000; 14: 859—870.

181.

Takayama K. , Qureshi N. , Raetz CR et al. Influence of fine structure of lipid A on Limulus amebocyte lysate clotting and toxic activities. Infect Immun 1984; 45: 350—355.

182.

Manthey CL , Qureshi N. , Stutz PL , Vogel SN Lipopolysaccharide antagonists block taxol-induced signaling in murine macrophages. J Exp Med 1993; 178: 695—702.

183.

Caldwell HD , Hitchcock PJ Monoclonal antibody against a genus-specific antigen of Chlamydia species: location of the epitope on chlamydial lipopolysaccharide . Infect Immun 1984; 44: 306—314.

184.

Wong KH , Moss CW , Hochstein DH , Arko RJ , Schalla WO `Endotoxicity' of the Legionnaires' disease bacterium. Ann Intern Med 1979; 90: 624—627.

185.

Janeway Jr CA The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol Today 1992; 13: 11—16.

186.

Newton RC Effect of interferon on the induction of human monocyte secretion of interleukin-1 activity. Immunology 1985; 56: 441—449.

187.

Gifford GE , Lohmann-Matthes ML. Gamma interferon priming of mouse and human macrophages for induction of tumor necrosis factor production by bacterial lipopolysaccharide . J Natl Cancer Inst 1987; 78: 121—124.

188.

Haas JG , Meyer N. , Riethmüller G. , Ziegler-Heitbrock HW Inhibition of lipopolysaccharide-induced in vitro desensitization by interferon-gamma . Eur J Immunol 1990; 20: 1181—1184.

189.

Hayes MP , Enterline JC , Gerrard TL , Zoon KC Regulation of interferon production by human monocytes: requirements for priming for lipopolysaccharide-induced production. J Leukoc Biol 1991; 50: 176—181.

190.

Hayes MP , Zoon KC Priming of human monocytes for enhanced lipopolysaccharide responses: expression of alpha interferon, interferon regulatory factors, and tumor necrosis factor . Infect Immun 1993; 61: 3222—3227.

191.

de Wit H. , Dokter WH , Esselink MT , Halie MR , Vellenga E. Interferon-gamma enhances the LPS-induced G-CSF gene expression in human adherent monocytes, which is regulated at transcriptional and posttranscriptional levels . Exp Hematol 1993; 21: 785—790.

192.

Hayes MP , Freeman SL , Donnelly RP IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and mRNA stability. Cytokine 1995; 7: 427—435.

193.

Visintin A. , Mazzoni A. , Spitzer JH , Wyllie DH , Dower SK , Segal DM Regulation of Toll-like receptors in human monocytes and dendritic cells. J Immunol 2001 ; 166: 249—255.

194.

Du X. , Poltorak A. , Silva M. , Beutler B. Analysis of TLR4-mediated LPS signal transduction in macrophages by mutational modification of the receptor. Blood Cells Mol Dis 1999; 25: 328—338.

195.

Mold C. , Gewurz H. , Du Clos TW Regulation of complement activation by C-reactive protein. Immunopharmacology 1999; 42: 23—30.

196.

de Haas CJ , van der Tol ME , Van Kessel KP , Verhoef J. , Van Strijp JA A synthetic lipopolysaccharide-binding peptide based on amino acids 27—39 of serum amyloid P component inhibits lipopolysaccharide-induced responses in human blood. J Immunol 1998; 161: 3607—3615.

197.

de Haas CJ , van Leeuwen EM , van Bommel T. , Verhoef J. , van Kessel KP , van Strijp JA Serum amyloid P component bound to Gram-negative bacteria prevents lipopolysaccharide-mediated classical pathway complement activation. Infect Immun 2000; 68: 1753—1759.

198.

Frey EA , Miller DS , Jahr TG et al. Soluble CD14 participates in the response of cells to lipopolysaccharide . J Exp Med 1992; 176: 1665—1671.

199.

Pugin J. , Schurer-Maly CC , Leturcq D. , Moriarty A. , Ulevitch RJ , Tobias PS Lipopolysaccharide activation of human endothelial and epithelial cells is mediated by lipopolysaccharide-binding protein and soluble CD14. Proc Natl Acad Sci USA 1993; 90: 2744—2748.

200.

Pugin J. , Ulevitch RJ , Tobias PS A critical role for monocytes and CD14 in endotoxin-induced endothelial cell activation. J Exp Med 1993; 178: 2193—2200.

201.

Golenbock DT , Bach RR , Lichenstein H. , Juan TS , Tadavarthy A. , Moldow CF Soluble CD14 promotes LPS activation of CD14-deficient PNH monocytes and endothelial cells. J Lab Clin Med 1995; 125: 662—671.

202.

Vita N. , Lefort S. , Sozzani P. et al. Detection and biochemical characteristics of the receptor for complexes of soluble CD14 and bacterial lipopolysaccharide. J Immunol 1997; 158: 3457—3462.

203.

Frantz S. , Kobzik L. , Kim YD et al. Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest 1999; 104: 271—280.

204.

Loppnow H. , Stelter F. , Schönbeck U. et al. Endotoxin activates human vascular smooth muscle cells despite lack of expression of CD14 mRNA or endogenous membrane CD14. Infect Immun 1995; 63: 1020—1026.

205.

Helfgott DC , May LT , Sthoeger Z. , Tamm I. , Sehgal PB Bacterial lipopolysaccharide (endotoxin) enhances expression and secretion of beta 2 interferon by human fibroblasts. J Exp Med 1987; 166: 1300—1309.

206.

Hayashi J. , Masaka T. , Saito I. , Ishikawa I. Soluble CD14 mediates lipopolysaccharide-induced intercellular adhesion molecule 1 expression in cultured human gingival fibroblasts . Infect Immun 1996; 64: 4946—4951.

207.

Tabeta K. , Yamazaki K. , Akashi S. et al. Toll-like receptors confer responsiveness to lipopolysaccharide from Porphyromonas gingivalis in human gingival fibroblasts. Infect Immun 2000; 68: 3731—3735.

208.

Cario E. , Rosenberg IM , Brandwein SL , Beck PL , Reinecker HC , Podolsky DK Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J Immunol 2000; 164: 966—972.

209.

Dinarello CA Immediate cytokine response to endotoxin: tumor necrosis factor-alpha and the interleukin-1 family. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease, New York: Marcel Dekker , 1999; 549—560.

210.

Suffredini AF , Fantuzzi G. , Badolato R. , Oppenheim JJ , O'Grady NP. New insights into the biology of the acute phase response. J Clin Immunol 1999; 19: 203—214.

211.

Whetton AD , Spooncer E. Role of cytokines and extracellular matrix in the regulation of haemopoietic stem cells. Curr Opin Cell Biol 1998; 10: 721—726.

212.

Osterud B. Cellular interactions in tissue factor expression by blood monocytes. Blood Coagul Fibrinolysis 1995; 6 (Suppl 1): S20—S25.

213.

Wada H. , Wakita Y. , Shiku H. Tissue factor expression in endothelial cells in health and disease. Blood Coagul Fibrinolysis 1995; 6 (Suppl 1): S26—S31.

214.

Okamura H. , Kashiwamura S. , Tsutsui H. , Yoshimoto T. , Nakanishi K. Regulation of interferon-gamma production by IL-12 and IL-18. Curr Opin Immunol 1998 ; 10: 259—264.

215.

Dinarello CA , Novick D. , Puren AJ et al. Overview of interleukin-18: more than an interferon-gamma inducing factor. J Leukoc Biol 1998; 63: 658—664.

216.

Michie HR , Manogue KR , Spriggs DR et al. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med 1988; 318: 1481—1486.

217.

Eskay RL , Grino M. , Chen HT Interleukins, signal transduction, and the immune system-mediated stress response . Adv Exp Med Biol 1990; 274: 331—343.

218.

Vedder H. , Schreiber W. , Yassouridis A. , Gudewill S. , Galanos C. , Pollmacher T. Dose-dependence of bacterial lipopolysaccharide (LPS) effects on peak response and time course of the immune-endocrine host response in humans. Inflamm Res 1999; 48: 67—74.

219.

Maier SF , Watkins LR Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychol Rev 1998; 105: 83—107.

220.

Watkins LR , Maier SF Implications of immune-to-brain communication for sickness and pain. Proc Natl Acad Sci USA 1999; 96: 7710—7713.

221.

Zeisberger E. , Roth J. Neurobiological concepts of fever generation and suppression. Neuropsychobiology 1993; 28: 106—109.

222.

Watkins LR , Goehler LE , Relton JK et al. Blockade of interleukin-1 induced hyperthermia by subdiaphragmatic vagotomy: evidence for vagal mediation of immune-brain communication. Neurosci Lett 1995; 183: 27—31.

223.

Blatteis CM , Sehic E. Cytokines and fever. Ann NY Acad Sci 1998; 840: 608—618.

224.

Borovikova LV , Ivanova S. , Zhang M. et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000; 405: 458—462.

225.

Gaykema RP , Dijkstra I. , Tilders FJ Subdiaphragmatic vagotomy suppresses endotoxin-induced activation of hypothalamic corticotropin-releasing hormone neurons and ACTH secretion. Endocrinology 1995; 136: 4717—4120.

226.

Woiciechowsky C. , Asadullah K. , Nestler D. et al. Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nat Med 1998; 4: 808—813.

227.

Scheinman RI , Cogswell PC , Lofquist AK , Baldwin Jr AS Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science 1995; 270: 283—286.

228.

Auphan N. , DiDonato JA , Rosette C. , Helmberg A. , Karin M. Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 1995; 270: 286—290.

229.

Joyce DA , Steer JH , Abraham LJ Glucocorticoid modulation of human monocyte/macrophage function: control of TNF-alpha secretion. Inflamm Res 1997; 46: 447—451.

230.

Calandra T. , Bernhagen J. , Mitchell RA , Bucala R. The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med 1994; 179: 1895—1902.

231.

Calandra T. , Bernhagen J. , Metz CN et al. MIF as a glucocorticoid-induced modulator of cytokine production. Nature 1995; 377: 68—71.

232.

Calandra T. , Bucala R. Macrophage migration inhibitory factor (MIF): a glucocorticoid counter-regulator within the immune system. Crit Rev Immunol 1997; 17: 77—88.

233.

Morand EF , Leech M. Glucocorticoid regulation of inflammation: the plot thickens. Inflamm Res 1999; 48: 557—560.

234.

Bozza M. , Satoskar AR , Lin G. et al. Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis. J Exp Med 1999 ; 189: 341—346.

235.

Calandra T. , Echtenacher B. , Roy DL et al. Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nat Med 2000; 6: 164—170.

236.

Beutler B. , Krochin N. , Milsark IW , Luedke C. , Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science 1986; 232: 977—980.

237.

Matic M. , Simon SR Tumor necrosis factor release from lipopolysaccharide-stimulated human monocytes: lipopolysaccharide tolerance in vitro. Cytokine 1991; 3: 576—583.

238.

Wittmann M. , Larsson VA , Schmidt P. , Begemann G. , Kapp A. , Werfel T. Suppression of interleukin-12 production by human monocytes after preincubation with lipopolysaccharide. Blood 1999; 94: 1717—1726.

239.

Mackensen A. , Galanos C. , Wehr U. , Engelhardt R. Endotoxin tolerance: regulation of cytokine production and cellular changes in response to endotoxin application in cancer patients. Eur Cytokine Netw 1992; 3: 571—579.

240.

Mengozzi M. , Ghezzi P. Cytokine down-regulation in endotoxin tolerance . Eur Cytokine Netw 1993; 4: 89—98.

241.

Ziegler-Heitbrock HW Molecular mechanism in tolerance to lipopolysaccharide . J Inflamm 1995; 45: 13—26.

242.

Schade FU , Flach R. , Flohe S. et al. Endotoxin tolerance. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease, New York: Marcel Dekker, 1999; 751—767.

243.

de Waal Malefyt R. , Abrams J. , Bennett B. , Figdor CG , de Vries JE Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes . J Exp Med 1991; 174: 1209—1220.

244.

Bogdan C. , Vodovotz Y. , Nathan C. Macrophage deactivation by interleukin 10. J Exp Med 1991; 174: 1549—1555.

245.

Fiorentino DF , Zlotnik A. , Mosmann TR , Howard M. , O'Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol 1991; 147: 3815—3822.

246.

Frankenberger M. , Pechumer H. , Ziegler-Heitbrock HW Interleukin-10 is upregulated in LPS tolerance. J Inflamm 1995; 45: 56—63.

247.

Randow F. , Syrbe U. , Meisel C. et al. Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta. J Exp Med 1995; 181: 1887—1892.

248.

Imai K. , Takeshita A. , Hanazawa S. TGF-beta inhibits lipopolysaccharide-stimulated activity of c-Jun N-terminal kinase in mouse macrophages. FEBS Lett 1999 ; 456: 375—378.

249.

Hart PH , Whitty GA , Piccoli DS , Hamilton JA Control by IFN-gamma and PGE2 of TNF alpha and IL-1 production by human monocytes . Immunology 1989; 66: 376—383.

250.

Tominaga K. , Saito S. , Matsuura M. , Nakano M. Lipopolysaccharide tolerance in murine peritoneal macrophages induces down-regulation of the lipopolysaccharide signal transduction pathway through mitogen-activated protein kinase and nuclear factor-kappaB cascades, but not lipopolysaccharide-incorporation steps. Biochim Biophys Acta 1999; 1450: 130—144.

251.

Chomarat P. , Rissoan MC , Banchereau J. , Miossec P. Interferon gamma inhibits interleukin 10 production by monocytes. J Exp Med 1993; 177: 523—527.

252.

Geiger T. , Arnold J. , Rordorf C. , Henn R. , Vosbeck K. Interferon-gamma overcomes the glucocorticoid-mediated and the interleukin-4-mediated inhibition of interleukin-1 beta synthesis in human monocytes. Lymphokine Cytokine Res 1993; 12: 271—278.

253.

Donnelly RP , Freeman SL , Hayes MP Inhibition of IL-10 expression by IFN-gamma up-regulates transcription of TNF-alpha in human monocytes. J Immunol 1995; 155: 1420—1427.

254.

Randow F. , Döcke WD , Bundschuh DS , Hartung T. , Wendel A. , Volk HD In vitro prevention and reversal of lipopolysaccharide desensitization by IFN-gamma, IL-12, and granulocyte-macrophage colony-stimulating factor. J Immunol 1997; 158: 2911—2918.

255.

Döcke WD , Randow F. , Syrbe U. et al. Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nat Med 1997; 3: 678—681.

256.

Medvedev AE , Kopydlowski KM , Vogel SN Inhibition of lipopolysaccharide-induced signal transduction in endotoxintolerized mouse macrophages: dysregulation of cytokine, chemokine, and Toll-like receptor 2 and 4. J Immunol 2000; 164: 5564—5574.

257.

Li L. , Cousart S. , Hu J. , McCall CE Characterization of IRAK in normal and endotoxin tolerant cells. J Biol Chem 2000; 275: 23340—23345.

258.

Akashi S. , Shimazu R. , Ogata H. et al. Cutting edge: cell surface expression and lipopolysaccharide signaling via the Toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages . J Immunol 2000; 164: 3471—3475.

259.

Nomura F. , Akashi S. , Sakao Y. et al. Cutting edge: endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface Toll-like receptor 4 expression . J Immunol 2000; 164: 3476—3479.

260.

Iwami K-I. , Matsuguchi T. , Masuda A. , Kikuchi T. , Musikacharoen T. , Yoshikai Y. Cutting edge: naturally occurring soluble form of mouse toll-like receptor 4 inhibits lipopolysaccharide signaling. J Immunol 2000; 165: 6682—6686.

261.

Hart PH , Vitti GF , Burgess DR , Whitty GA , Piccoli DS , Hamilton JA Potential anti-inflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2 . Proc Natl Acad Sci USA 1989; 86: 3803—3807.

262.

te Velde AA , Huijbens RJ , Heije K. , de Vries JE , Figdor CG Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. Blood 1990; 76: 1392—1397.

263.

Marchant A. , Bruyns C. , Vandenabeele P. et al. Interleukin-10 controls interferon-gamma and tumor necrosis factor production during experimental endotoxemia. Eur J Immunol 1994; 24: 1167—1171.

264.

Trepicchio WL , Bozza M. , Pedneault G. , Dorner AJ Recombinant human IL-11 attenuates the inflammatory response through down-regulation of proinflammatory cytokine release and nitric oxide production. J Immunol 1996; 157: 3627—3634.

265.

Minty A. , Chalon P. , Derocq JM et al. Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature 1993; 362: 248—250.

266.

de Waal Malefyt R. , Figdor CG , Huijbens R. et al. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. J Immunol 1993; 151: 6370—6381.

267.

Evans GF , Zuckerman SH Glucocorticoid-dependent and- independent mechanisms involved in lipopolysaccharide tolerance. Eur J Immunol 1991; 21: 1973—1979.

268.

Galanos C. , Freudenberg MA Mechanisms of endotoxin shock and endotoxin hypersensitivity. Immunobiology 1993; 187: 346—56.

269.

Freudenberg MA , Merlin T. , Sing A. , Galanos C. Bacteria-induced hypersensitivity to endotoxin . In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease, New York: Marcel Dekker , 1999; 719—733.

270.

Opal SM The value of animal models in endotoxin research. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease, New York : Marcel Dekker, 1999; 809—816.

271.

Redl H. , Schlag G. , Bahrami S. Endotoxemia in primate models. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease, New York: Marcel Dekker, 1999; 795—808.

272.

Suffredini AF , O'Grady NP Pathophysiological responses to endotoxin in humans. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease, New York: Marcel Dekker , 1999; 817—830.

273.

Poltorak A. , He X. , Smirnova I. et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998; 282: 2085—2088.

274.

Qureshi ST , Lariviare L. , Leveque G. et al. Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J Exp Med 1999; 189: 615—625.

275.

Smirnova I. , Poltorak A. , Chan Ekl , McBride C. , Beutler B. Phylogenetic variation and polymorphism at the Toll-like receptor 4 locus (TLR4). Genome Biol 2000; 1: Research002.1-002.10 ( http://genomebiology.com).

276.

Arbour NC , Lorenz E. , Schütte BC et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 2000; 25: 187—191.

277.

O'Neill LA , Greene C. Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants. J Leukoc Biol 1998; 63: 650—657.

278.

Bowie A. , O'Neill LA The interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-inflammatory interleukins and microbial products. J Leukoc Biol 2000; 67: 508—514.

279.

Ingalls RR , Golenbock DT CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide. J Exp Med 1995; 181: 1473—1479.

280.

Flaherty SF , Golenbock DT , Milham FH , Ingalls RR CD11/CD18 leukocyte integrins: new signaling receptors for bacterial endotoxin. J Surg Res 1997; 73: 85—89.

281.

Ingalls RR , Arnaout MA , Golenbock DT Outside-in signaling by lipopolysaccharide through a tailless integrin. J Immunol 1997 ; 159: 433—438.

282.

Ingalls RR , Monks BG , Savedra Jr R. et al. CD11/CD18 and CD14 share a common lipid A signaling pathway. J Immunol 1998; 161: 5413—5420.

283.

Perera P-Y. , Mayadas TN , Takeuchi O. et al. CD11b/CD18 acts in concert with CD14 and Toll-like receptor (TLR) 4 to elicit full lipopolysaccharide and Taxol-inducible gene expression. J Immunol 2001; 166: 574—581.

284.

el-Samalouti VT , Schletter J. , Chyla I. et al. Identification of the 80-kDa LPS-binding protein (LMP80) as decay-accelerating factor (DAF, CD55). FEMS Immunol Med Microbiol 1999; 23: 259—269.

285.

Ulmer AJ , Heine H. , El-Samalouti VT et al. Decay accelerating factor (DAF/CD55) is a functional active element of the LPS receptor complex. J Endotoxin Res 2000, 6: 79.

286.

Tohme ZN , Amar S. , Van Dyke TE Moesin functions as a lipopolysaccharide receptor on human monocytes. Infect Immun 1999; 67: 3215—3220.

287.

Tohme ZN , Amar S. , Van Dyke TE Moesin: a potential LPS receptor on human monocytes. J Endotoxin Res 2000, 6: 79.

288.

Tobias PS , Soldau K. , Ulevitch RJ Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J Exp Med 1986; 164: 777—793.

289.

Wright SD , Tobias PS , Ulevitch RJ , Ramos RA Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages. J Exp Med 1989; 170: 1231—1241.

290.

Kitchens RL , Munford RS CD14-dependent internalization of bacterial lipopolysaccharide (LPS) is strongly influenced by LPS aggregation but not by cellular responses to LPS. J Immunol 1998 ; 160: 1920—1928.

291.

Ferrero E. , Goyert SM Nucleotide sequence of the gene encoding the monocyte differentiation antigen, CD14. Nucleic Acids Res 1988; 16: 4173.

292.

Ferrero E. , Hsieh CL , Francke U. , Goyert SM CD14 is a member of the family of leucine-rich proteins and is encoded by a gene syntenic with multiple receptor genes. J Immunol 1990; 145: 331—336.

293.

Schumann RR , Leong SR , Flaggs GW et al. Structure and function of lipopolysaccharide binding protein. Science 1990; 249: 1429—1431.

294.

Wright SD , Ramos RA , Tobias PS , Ulevitch RJ , Mathison JC CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 1990; 249: 1431—1433.

295.

Hailman E. , Lichenstein HS , Wurfel MM et al. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med 1994; 179: 269—277.

296.

Tobias PS , Soldau K. , Gegner JA , Mintz D. , Ulevitch RJ Lipopolysaccharide binding protein-mediated complexation of lipopolysaccharide with soluble CD14. J Biol Chem 1995; 270: 10482—10488.

297.

Gallay P. , Heumann D. , Le Roy D. , Barras C. , Glauser MP Lipopolysaccharide-binding protein as a major plasma protein responsible for endotoxemic shock. Proc Natl Acad Sci USA 1993; 90: 9935—9938.

298.

Hailman E. , Vasselon T. , Kelley M. et al. Stimulation of macrophages and neutrophils by complexes of lipopolysaccharide and soluble CD14. J Immunol 1996; 156: 4384—4390.

299.

Jack RS , Fan X. , Bernheiden M. et al. Lipopolysaccharide-binding protein is required to combat a murine Gram-negative bacterial infection. Nature 1997; 389: 742—745.

300.

Wurfel MM , Monks BG , Ingalls RR et al. Targeted deletion of the lipopolysaccharide (LPS)-binding protein gene leads to profound suppression of LPS responses ex vivo, whereas in vivo responses remain intact. J Exp Med 1997; 186: 2051—2056.

301.

Tobias PS Lipopolysaccharide binding protein. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease, New York: Marcel Dekker, 1999; 359—367.

302.

Schumann RR , Latz E. Lipopolysaccharide-binding protein. Chem Immunol 2000; 74: 42—60.

303.

Tapping RI , Tobias PS Soluble CD14-mediated cellular responses to lipopolysaccharide. Chem Immunol 2000;74: 108—121.

304.

Beamer LJ , Carroll SF , Eisenberg D. Crystal structure of human BPI and two bound phospholipids at 2.4 Angstrom resolution. Science 1997; 276: 1861—1864.

305.

Beamer LJ , Carroll SF , Eisenberg D. The BPI/LBP family of proteins: a structural analysis of conserved regions . Protein Sci 1998; 7: 906—914.

306.

Weiss J. , Elsbach P. , Olsson I. , Odeberg H. Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. J Biol Chem 1978; 253: 2664—2672.

307.

Elsbach P. The bactericidal/permeability-increasing protein (BPI) in antibacterial host defense. J Leukoc Biol 1998, 64: 14—18.

308.

Gazzano-Santoro H. , Parent JB , Grinna L. et al. High-affinity binding of the bactericidal/permeability-increasing protein and a recombinant amino-terminal fragment to the lipid A region of lipopolysaccharide. Infect Immun 1992; 60: 4754—4761.

309.

Appelmelk BJ , An YQ , Thijs BG , MacLaren DM , de Graaff J. Recombinant human bactericidal/permeability-increasing protein (rBPI23) is a universal lipopolysaccharide-binding ligand. Infect Immun 1994; 62: 3564—3567.

310.

Theofan G. , Horwitz AH , Williams RE et al. An amino-terminal fragment of human lipopolysaccharide-binding protein retains lipid A binding but not CD14-stimulatory activity. J Immunol 1994; 152: 3623—3629.

311.

Abrahamson SL , Wu HM , Williams RE et al. Biochemical characterization of recombinant fusions of lipopolysaccharide binding protein and bactericidal/permeability-increasing protein. Implications in biological activity. J Biol Chem 1997; 272: 2149—2155.

312.

Vasselon T. , Hailman E. , Thieringer R. , Detmers PA Internalization of monomeric lipopolysaccharide occurs after transfer out of cell surface CD14. J Exp Med 1999; 190: 509—522.

313.

Lee JD , Kato K. , Tobias PS , Kirkland TN , Ulevitch RJ Transfection of CD14 into 70Z/3 cells dramatically enhances the sensitivity to complexes of lipopolysaccharide (LPS) and LPS binding protein. J Exp Med 1992; 175: 1697—1705.

314.

Golenbock DT , Liu Y. , Millham FH , Freeman MW , Zoeller RA Surface expression of human CD14 in Chinese hamster ovary fibroblasts imparts macrophage-like responsiveness to bacterial endotoxin. J Biol Chem 1993; 268: 22055—22059.

315.

Couturier C. , Jahns G. , Kazatchkine MD , Haeffner-Cavaillon N. Membrane molecules which trigger the production of interleukin-1 and tumor necrosis factor-alpha by lipopolysaccharide-stimulated human monocytes. Eur J Immunol 1992; 22: 1461—1466.

316.

Heumann D. , Gallay P. , Barras C. et al. Control of lipopolysaccharide (LPS) binding and LPS-induced tumor necrosis factor secretion in human peripheral blood monocytes. J Immunol 1992; 148: 3505—3512.

317.

Gallay P. , Jongeneel CV , Barras C. et al. Short time exposure to lipopolysaccharide is sufficient to activate human monocytes. J Immunol 1993; 150: 5086—5093.

318.

Haziot A. , Ferrero E. , Kontgen F. et al. Resistance to endotoxin shock and reduced dissemination of Gram-negative bacteria in CD14-deficient mice. Immunity 1996; 4: 407—414.

319.

Yu B. , Wright SD Catalytic properties of lipopolysaccharide (LPS) binding protein. Transfer of LPS to soluble CD14. J Biol Chem 1996; 271: 4100—4105.

320.

Gegner JA , Ulevitch RJ , Tobias PS Lipopolysaccharide (LPS) signal transduction and clearance. Dual roles for LPS binding protein and membrane CD14. J Biol Chem 1995; 270: 5320—5325.

321.

Schiff DE , Kline L. , Soldau K. et al. Phagocytosis of Gram-negative bacteria by a unique CD14-dependent mechanism. J Leukoc Biol 1997; 62: 786—794.

322.

Jack RS , Grünwald U. , Stelter F. , Workalemahu G. , Schütt C. Both membrane-bound and soluble forms of CD14 bind to Gram-negative bacteria . Eur J Immunol 1995; 25: 1436—1441.

323.

Schütt C. , Bernheiden M. , Grünwald U. et al. Implications for a general role of LPS-binding proteins (CD14, LBP) in combating bacterial infections. J Endotoxin Res 1999, 5: 75—80.

324.

Kitchens RL , Munford RS Internalization of lipopolysaccharide by phagozytes. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease, New York : Marcel Dekker, 1999; 521—535.

325.

Antal-Szalmas P. , Strijp JA , Weersink AJ , Verhoef J. , Van Kessel KP. Quantitation of surface CD14 on human monocytes and neutrophils. J Leukoc Biol 1997 ; 61: 721—728.

326.

Marchant A. , Duchow J. , Delville JP , Goldman M. Lipopolysaccharide induces up-regulation of CD14 molecule on monocytes in human whole blood. Eur J Immunol 1992; 22: 1663—1665.

327.

Landmann R. , Knopf HP , Link S. , Sansano S. , Schumann R. , Zimmerli W. Human monocyte CD14 is upregulated by lipopolysaccharide . Infect Immun 1996; 64: 1762—1769.

328.

Matsuura K. , Ishida T. , Setoguchi M. , Higuchi Y. , Akizuki S. , Yamamoto S. Upregulation of mouse CD14 expression in Kupffer cells by lipopolysaccharide. J Exp Med 1994 ; 179: 1671—1676.

329.

Weingarten R. , Sklar LA , Mathison JC et al. Interactions of lipopolysaccharide with neutrophils in blood via CD14. J Leukoc Biol 1993; 53: 518—524.

330.

Fearns C. , Ulevitch RJ Effect of recombinant interleukin-1beta on murine CD14 gene expression in vivo. Shock 1998; 9: 157—163.

331.

Devitt A. , Moffatt OD , Raykundalia C. , Capra JD , Simmons DL , Gregory CD Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 1998; 392: 505—509.

332.

Gregory CD Non-inflammatory/anti-inflammatory CD14 responses: CD14 in apoptosis. Chem Immunol 2000; 74: 122—140.

333.

Schneider R. , Schneider-Scherzer E. , Thurnher M. , Auer B. , Schweiger M. The primary structure of human ribonuclease/angiogenin inhibitor (RAI) discloses a novel highly diversified protein superfamily with a common repetitive module. EMBO J 1988; 7: 4151—4156.

334.

Kobe B. , Deisenhofer J. The leucine-rich repeat: a versatile binding motif. Trends Biochem Sci 1994; 19: 415—421.

335.

Medzhitov R. , Preston-Hurlburt P. , Janeway Jr CA. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity . Nature 1997; 388: 394—397.

336.

Rock FL , Hardiman G. , Timans JC , Kastelein RA , Bazan JF A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci USA 1998; 95: 588—593.

337.

Chaudhary PM , Ferguson C. , Nguyen V. et al. Cloning and characterization of two Toll/interleukin-1 receptor-like genes TIL3 and TIL4: evidence for a multi-gene receptor family in humans. Blood 1998; 91: 4020—4027.

338.

Takeuchi O. , Kawai T. , Sanjo H. et al. TLR6: a novel member of an expanding Toll-like receptor family. Gene 1999; 231: 59—65.

339.

Hardiman GT , Rock FL , Bazan JF , Kastelein RA Human Toll-like receptor proteins, related reagents and methods. Patent application number: WO9850547A2 and A3; 1998. URL: http://patent.womplex.ibm.com

340.

Du X. , Poltorak A. , Wei Y. , Beutler B. Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw 2000; 11: 362—371.

341.

Chuang TH , Ulevitch RJ Cloning and characterization of a subfamily of human toll-like receptors: hTLR7, hTLR8 and hTLR9. Eur Cytokine Netw 2000; 11: 372—378.

342.

Hoshino K. , Takeuchi O. , Kawai T. et al. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the lps gene product. J Immunol 1999 ; 162: 3749—3752.

343.

Rehli M. , Poltorak A. , Schwarzfischer L. , Krause SW , Andreesen R. , Beutler B. PU.1 and interferon consensus sequence-binding protein regulate the myeloid expression of the human Toll-like receptor 4 gene. J Biol Chem 2000; 275: 9773—9781.

344.

Ozinsky A. , Underhill DM , Fontenot JD et al. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors. Proc Natl Acad Sci USA 2000; 97: 13766—13771.

345.

Hemmi H. , Takeuchi O. , Kawai T. et al. A Toll-like receptor recognizes bacterial DNA. Nature 2000; 408: 740—745.

346.

Sultzer BM Genetic control of leucocyte responses to endotoxin. Nature 1968; 219: 1253—1254.

347.

Watson J. , Riblet R. Genetic control of responses to bacterial lipopolysaccharides in mice. I. Evidence for a single gene that influences mitogenic and immunogenic response to lipopolysaccharides. J Exp Med 1974; 140: 1147—1161.

348.

Vogel SN , Johnson D. , Perera PY et al. Cutting edge: functional characterization of the effect of the C3H/HeJ defect in mice that lack an lpsn gene: In vivo evidence for a dominant negative mutation. J Immunol 1999; 162: 5666—5670.

349.

Coutinho A. , Meo T. Genetic basis for unresponsiveness to lipopolysaccharide in C57BL/10Cr mice. Immunogenetics 1978; 7: 17—24.

350.

Poltorak A. , Smirnova I. , Clisch R. , Beutler B. Limits of a deletion spanning TLR4 in C57BL/10ScCr mice. J Endotoxin Res 2000; 6: 51—56.

351.

Rhee SH , Hwang D. Murine Toll-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF-kappaB and expression of the inducible cylcooxygenase . J Biol Chem 2000; 275: 34035—34040.

352.

Takeuchi O. , Hoshino K. , Kawai T. et al. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components . Immunity 1999; 11: 443—451. 353. Takeuchi O. , Takeda K. , Hoshino K. , Adachi O. , Ogawa T. , Akira S. Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades. Int Immunol 2000; 12: 113—117.

353.

Hirschfeld M. , Ma Y. , Weis JH , Vogel SN , Weis JJ Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine Toll-like receptor 2. J Immunol 2000; 165: 618—622.

354.

Shimazu R. , Akashi S. , Ogata H. et al. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 1999; 189: 1777—1782.

355.

Akashi S. , Ogata H. , Kirikae F. et al. Regulatory roles for CD14 and phosphatidylinositol in the signaling via Toll-like receptor 4-MD-2. Biochem Biophys Res Commun 2000; 268: 172—177.

356.

Yang H. , Young DW , Gusovsky F. , Chow JC Cellular events mediated by lipopolysaccharide-stimulated Toll-like receptor 4. MD-2 is required for activation of mitogen-activated protein kinases and Elk-1. J Biol Chem 2000; 275 :20861—20866.

357.

da Silva J. , Soldau K. , Tobias P. , Ulevitch R. LPS binds to a multiprotein receptor: transfer from LBP-CD14 to TLR4-MD-2. J Biol Chem 2001 ; 276: 21129—21135.

358.

Kobe B. , Deisenhofer J. Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats. Nature 1993; 366: 751—756.

359.

Kobe B. , Deisenhofer J. A structural basis of the interactions between leucine-rich repeats and protein ligands. Nature 1995; 374: 183—186. 361. Papageorgiou AC , Shapiro R. , Acharya KR Molecular recognition of human angiogenin by placental ribonuclease inhibitor — an X-ray crystallographic study at 2.0 Å resolution. EMBO J 1997; 16: 5162—5177.

360.

Ding AH , Porteu F. , Sanchez E. , Nathan CF Shared actions of endotoxin and taxol on TNF receptors and TNF release. Science 1990; 248: 370—372.

361.

Kawasaki K. , Akashi S. , Shimazu R. , Yoshida T, Miyake K, Nishijima M. Mouse Toll-like receptor 4*MD-2 complex mediates lipopolysaccharide-mimetic signal transduction by Taxol. J Biol Chem 2000; 275: 2251—2254.

362.

Kirikae F. , Kirikae T. , Qureshi N. , Takayama K. , Morrisson DC , Nakano M. CD14 is not involved in Rhodobacter sphaeroides diphosphoryl lipid A inhibition of tumor necrosis factor alpha and nitric oxide induction by taxol in murine macrophages. Infect Immun 1995; 63: 486—497.

363.

Perera PY , Vogel SN , Detore GR , Haziot A. , Goyert SM CD14-dependent and CD14-independent signaling pathways in murine macrophages from normal and CD14 knockout mice stimulated with lipopolysaccharide or Taxol . J Immunol 1997; 158: 4422—4429. 366. Medzhitov R. , Preston-Hurlburt P. , Kopp E. et al. MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol Cell 1998; 2: 253—258.

364.

Muzio M. , Natoli G. , Saccani S. , Levrero M. , Mantovani A. The human Toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6). J Exp Med 1998; 187: 2097—2101.

365.

Kawai T. , Adachi O. , Ogawa T. , Takeda K. , Akira S. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 1999; 11: 115—122. 369. Adachi O. , Kawai T. , Takeda K. et al. Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 1998 ; 9: 143—150.

366.

Swantek JL , Tsen MF , Cobb MH , Thomas JA IL-1 receptor-associated kinase modulates host responsiveness to endotoxin. J Immunol 2000; 164: 4301—4306.

367.

Wesche H. , Gao X. , Li X. , Kirschning CJ , Stark GR , Cao Z. IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem 1999; 274: 19403—19410. 372. Baker B. , Zambryski P. , Staskawicz B. , Dinesh-Kumar SP Signaling in plant-microbe interactions. Science 1997 ; 276: 726—733. 373. Sweet MJ , Hume DA Endotoxin signal transduction in macrophages. J Leukoc Biol 1996; 60: 8—26.

368.

Dziarski R. , Ulmer AJ , Gupta D. Interactions of CD14 with components of Gram-positive bacteria. Chem Immunol 2000; 74: 83—107. 375. Hultmark . D. Macrophage differentiation marker MyD88 is a member of the Toll/IL-1 receptor family. Biochem Biophys Res Commun 1994; 199: 144—146.

369.

Hardiman G. , Rock FL , Balasubramanian S. , Kastelein RA , Bazan JF Molecular characterization and modular analysis of human MyD88. Oncogene 1996; 13: 2467—2475.

370.

Bonnert TP , Garka KE , Parnet P. , Sonoda G. , Testa JR , Sims JE The cloning and characterization of human MyD88: a member of an IL-1 receptor related family. FEBS Lett 1997; 402: 81—84. 378. Wesche H. , Henzel WJ , Shillinglaw W. , Li S. , Cao Z. MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 1997; 7: 837—847.

371.

Muzio M. , Ni J. , Feng P. , Dixit VM IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 1997; 278: 1612—1615.

372.

Thomassen E. , Bird TA , Renshaw BR , Kennedy MK , Sims JE Binding of interleukin-18 to the interleukin-1 receptor homologous receptor IL-1Rrp1 leads to activation of signaling pathways similar to those used by interleukin-1. J Interferon Cytokine Res 1998; 18: 1077—1088.

373.

Schnare M. , Holtdagger AC , Takeda K. , Akira S. , Medzhitov R. Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Curr Biol 2000; 10: 1139—1142.

374.

Cao Z. , Henzel WJ , Gao X. IRAK: a kinase associated with the interleukin-1 receptor. Science 1996; 271: 1128—1131. 383. Shelton CA , Wasserman SA Pelle encodes a protein kinase required to establish dorsoventral polarity in the Drosophila embryo. Cell 1993; 72: 515—525.

375.

Loh YT , Martin GB The disease-resistance gene Pto and the fenthion-sensitivity gene fen encode closely related functional protein kinases. Proc Natl Acad Sci USA 1995; 92: 4181—4184.

376.

Kanakaraj P. , Schafer PH , Cavender DE et al. Interleukin (IL)-1 receptor-associated kinase (IRAK) requirement for optimal induction of multiple IL-1 signaling pathways and IL-6 production . J Exp Med 1998; 187: 2073—2079.

377.

Cao Z. , Xiong J. , Takeuchi M. , Kurama T. , Goeddel DV TRAF6 is a signal transducer for interleukin-1. Nature 1996; 383: 443—446.

378.

Arch RH , Gedrich RW , Thompson CB Tumor necrosis factor receptor-associated factors (TRAFs) — a family of adapter proteins that regulates life and death. Genes Dev 1998; 12: 2821—2830.

379.

Lomaga MA , Yeh WC , Sarosi I. et al. TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 1999; 13: 1015—1024.

380.

Lee FS , Hagler J. , Chen ZJ , Maniatis T. Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway. Cell 1997; 88: 213—222.

381.

Ninomiya-Tsuji J. , Kishimoto K. , Hiyama A. , Inoue J. , Cao Z. , Matsumoto K. The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 1999; 398: 252—256.

382.

Irie T. , Muta T. , Takeshige K. TAK1 mediates an activation signal from Toll-like receptor(s) to nuclear factor-kappaB in lipopolysaccharide-stimulated macrophages. FEBS Lett 2000; 467: 160—164.

383.

Mochida Y. , Takeda K. , Saitoh M. et al. ASK1 inhibits IL-1-induced NF-kappaB activity through disruption of TRAF6-TAK1 interaction. J Biol Chem 2000; 275: 32747—32752.

384.

Malinin NL , Boldin MP , Kovalenko AV , Wallach D. MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1. Nature 1997 ; 385: 540—544.

385.

Sanz L. , Diaz-Meco MT , Nakano H. , Moscat J. The atypical PKCinteracting protein p62 channels NF-kappaB activation by the IL-1TRAF6 pathway. EMBO J 2000; 19: 1576—1586.

386.

Kopp E. , Medzhitov R. , Carothers J. et al. ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway. Genes Dev 1999 ; 13: 2059—2071.

387.

Mercurio F. , Manning AM Multiple signals converging on NF-kappaB. Curr Opin Cell Biol 1999; 11: 226—232.

388.

Israel A.

The IKK complex: an integrator of all signals that activate NF-kappaB?

Trends Cell Biol 2000; 10: 129—133.

389.

Hatada EN , Krappmann D. , Scheidereit C. NF-kappaB and the innate immune response. Curr Opin Immunol 2000; 12: 52—58.

390.

Hawiger J. , Veach RA , Liu XY , Timmons S. , Ballard DW IkappaB kinase complex is an intracellular target for endotoxic lipopolysaccharide in human monocytic cells. Blood 1999; 94: 1711—1716.

391.

Garrington TP , Johnson GL Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr Opin Cell Biol 1999; 11: 211—218.

392.

Lee FS , Peters RT , Dang LC , Maniatis T. MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta. Proc Natl Acad Sci USA 1998; 95: 9319—9324.

393.

Nemoto S. , DiDonato JA , Lin A. Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase. kinase 1 and NF-kappaB-inducing kinase. Mol Cell Biol 1998; 18: 7336—7343.

394.

Zhao Q. , Lee FS Mitogen-activated protein kinase/ERK kinase kinases 2 and 3 activate nuclear factor-kappaB through IkappaB kinase-alpha and IkappaB kinase-beta. J Biol Chem 1999; 274: 8355—8358.

395.

Shirakabe K. , Yamaguchi K. , Shibuya H. et al. TAK1 mediates the ceramide signaling to stress-activated protein kinase/c-Jun N-terminal kinase. J Biol Chem 1997; 272: 8141—8144.

396.

Moriguchi T. , Kuroyanagi N. , Yamaguchi K. et al. A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. J Biol Chem 1996; 271: 13675—13679.

397.

Aliprantis AO , Yang RB , Mark MR et al. Cell activation and apoptosis by bacterial lipoproteins through Toll-like receptor-2. Science 1999; 285: 736—739.

398.

Aliprantis AO , Yang RB , Weiss DS , Godowski P. , Zychlinsky A. The apoptotic signaling pathway activated by Toll-like receptor-2. EMBO J 2000; 19: 3325—3336.

399.

Herrera-Velit P. , Reiner NE Bacterial lipopolysaccharide induces the association and coordinate activation of p53/56lyn and phosphatidylinositol 3-kinase in human monocytes. J Immunol 1996; 156: 1157—1165.

400.

Herrera-Velit P. , Knutson KL , Reiner NE Phosphatidylinositol 3-kinase-dependent activation of protein kinase C-zeta in bacterial lipopolysaccharide-treated human monocytes . J Biol Chem 1997; 272: 16445—16452.

401.

Reddy SA , Huang JH , Liao WS Phosphatidylinositol 3-kinase in interleukin 1 signaling. Physical interaction with the interleukin 1 receptor and requirement in NF-kappaB and AP-1 activation . J Biol Chem 1997; 272: 29167—29173.

402.

Marmiroli S. , Bavelloni A. , Faenza I. et al. Phosphatidylinositol 3-kinase is recruited to a specific site in the activated IL-1 receptor I. FEBS Lett 1998; 438: 49—54.

403.

Procyk KJ , Kovarik P. , von Gabain A. , Baccarini M. Salmonella typhimurium and lipopolysaccharide stimulate extracellularly regulated kinase activation in macrophages by a mechanism involving phosphatidylinositol 3-kinase and phospholipase D as novel intermediates. Infect Immun 1999; 67: 1011—1017.

404.

Jakway JP , DeFranco AL Pertussis toxin inhibition of B cell and macrophage responses to bacterial lipopolysaccharide. Science 1986; 234: 743—746.

405.

Zhang X. , Morrison DC Pertussis toxin-sensitive factor differentially regulates lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production in mouse peritoneal macrophages. J Immunol 1993; 150: 1011—1018.

406.

Zhang S. , Han J. , Sells MA et al. Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pak1. J Biol Chem 1995; 270: 23934—23936.

407.

Frost JA , Swantek JL , Stippec S. , Yin MJ , Gaynor R. , Cobb MH Stimulation of NF-kappaB activity by multiple signaling pathways requires PAK1. J Biol Chem 2000; 275: 19693—19693.

408.

Beaty CD , Franklin TL , Uehara Y. , Wilson CB Lipopolysaccharide-induced cytokine production in human monocytes: role of tyrosine phosphorylation in transmembrane signal transduction. Eur J Immunol 1994; 24: 1278—1284.

409.

Schromm AB , Brandenburg K. , Blunck R. et al. A biophysical approach towards an understanding of endotoxin-induced signal transduction. J Endotoxin Res 1999; 5: 41—45.

410.

Blunk R. , Scheel O. , Müller M. , Brandenburg K. , Seitzer U. , Seydel U. New insights into endotoxin-induced activation of macrophages: involvement of a K+-channel in transmembrane signaling, J Immunol 2001; In press.

411.

Lemaitre B. , Nicolas E. , Michaut L. , Reichhart JM , Hoffmann JA The dorsoventral regulatory gene cassette Spaetzle/Toll/Cactus controls the potent antifungal response in Drosophila adults. Cell 1996; 86: 973—983.

412.

DeLotto Y. , DeLotto R. Proteolytic processing of the Drosophila Spaetzle protein by Easter generates a dimeric NGF-like molecule with ventralising activity. Mech Dev 1998; 72: 141—148.

413.

Levashina EA , Langley E. , Green C. et al. Constitutive activation of Toll-mediated antifungal defense in serpin-deficient Drosophila. Science 1999; 285: 1917—1919.

414.

Underhill DM , Ozinsky A. , Hajjar AM et al. The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 1999; 401: 811—815.

415.

Inohara N. , Ogura Y. , Chen FF, Muto A, Nunez G. Human Nod1 confers responsiveness to bacterial lipopolysaccharides. J Biol Chem 2000; In press.

416.

Ogura Y. , Inohara N. , Benito A. , Chen FF , Yamaoka S. , Nunez G. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem 2000; In press.

417.

Inohara N. , Koseki T. , del Peso L. et al. Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB . J Biol Chem 1999; 274: 14560—14567.

418.

Bertin J. , Nir WJ , Fischer CM et al. Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-kappaB. J Biol Chem 1999; 274: 12955—12958.

419.

Ellis J. , Dodds P. , Pryor T. Structure, function and evolution of plant disease resistance genes. Curr Opin Plant Biol 2000; 3: 278—284.

420.

van Dissel JT , van Langevelde P. , Westendorp RG , Kwappenberg K. , Frölich M. Anti-inflammatory cytokine profile and mortality in febrile patients. Lancet 1998; 351: 950—953.

421.

Volk HD , Reinke P. , Döcke WD Clinical aspects: from systemic inflammation to `immunoparalysis'. Chem Immunol 2000; 74: 162—177.

422.

Brun-Buisson C. , Doyon F. , Carlet J. Bacteremia and severe sepsis in adults: a multicenter prospective survey in ICUs and wards of 24 hospitals. French Bacteremia-Sepsis Study Group. Am J Respir Crit Care Med 1996 ; 154: 617—624.

423.

Bellingan G. Inflammatory cell activation in sepsis. Br Med Bull 1999; 55: 12—29.

424.

Danner RL , Elin RJ , Hosseini JM , Wesley RA , Reilly JM , Parillo JE Endotoxemia in human septic shock. Chest 1991 ; 99: 169—175.

425.

Casey LC , Balk RA , Bone RC Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med 1993; 119: 771—778.

426.

Opal SM , Scannon PJ , Vincent JL et al. Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock. J Infect Dis 1999; 180: 1584—1589.

427.

Jacob AI , Goldberg PK , Bloom N. , Degenshein GA , Kozinn PJ Endotoxin and bacteria in portal blood. Gastroenterology 1977; 72: 1268—1270.

428.

Ruiter DJ , van der Meulen J. , Brouwer A. et al. Uptake by liver cells of endotoxin following its intravenous injection. Lab Invest 1981; 45: 38—45.

429.

Freudenberg MA , Galanos C. Bacterial lipopolysaccharides: structure, metabolism and mechanisms of action. Int Rev Immunol 1990; 6: 207—221.

430.

Novitzky TJ Endotoxin detection in body fluids: chemical versus bioassay methodology. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease, New York: Marcel Dekker, 1999; 831—839.

431.

Brandtzaeg P. , Kierulf P. , Gaustad P. et al. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease. J Infect Dis 1989; 159: 195—204.

432.

Beutler B. , Milsark IW , Cerami AC Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 1985; 229: 869—871.

433.

Wakabayashi G. , Gelfand JA , Burke JF , Thompson RC , Dinarello CA A specific receptor antagonist for interleukin 1 prevents Escherichia coli-induced shock in rabbits. FASEB J 1991; 5: 338—343.

434.

McIntyre KW , Stepan GJ , Kolinsky KD et al. Inhibition of interleukin 1 (IL-1) binding and bioactivity in vitro and modulation of acute inflammation in vivo by IL-1 receptor antagonist and anti-IL-1 receptor monoclonal antibody. J Exp Med 1991; 173: 931—939.

435.

Natanson C. , Hoffman WD , Suffredini AF , Eichacker PQ , Danner RL Selected treatment strategies for septic shock based on proposed mechanisms of pathogenesis. Ann Intern Med 1994; 120: 771—783.

436.

Zeni F. , Freeman B. , Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment . Crit Care Med 1997; 25: 1095—1100.

437.

Abraham E. Why immunomodulatory therapies have not worked in sepsis. Intensive Care Med 1999; 25: 556—566.

438.

Deitch EA Animal models of sepsis and shock: a review and lessons learned. Shock 1998; 9: 1—11.

439.

Baumgartner JD , Calandra T. Treatment of sepsis: past and future avenues . Drugs 1999; 57: 127—132.

440.

Opal SM , Yu Jr RL Antiendotoxin strategies for the prevention and treatment of septic shock. New approaches and future directions. Drugs 1998; 55: 497—508.

441.

Giroir BP , Quint PA , Barton P. et al. Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis. Lancet 1997; 350: 1439—1443.

442.

Levin M. , Quint PA , Goldstein B. et al. and the rBPI21 Meningococcal Sepsis Study Group. Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. Lancet 2000; 356: 961—967.

443.

Demetriades D. , Smith JS , Jacobson LE et al. Bactericidal/permeability-increasing protein (rBPI21) in patients with hemorrhage due to trauma: results of a multicenter phase II clinical trial. rBPI21 Acute Hemorrhagic Trauma Study Group. J Trauma 1999; 46: 667—676.

444.

Bunnell E. , Lynn M. , Habet K. et al. A lipid A analog, E5531, blocks the endotoxin response in human volunteers with experimental endotoxemia. Crit Care Med 2000; 28: 2713—2720.

445.

Smith OP , White B. , Vaughan D. et al. Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans. Lancet 1997; 350: 1590—1593.

446.

White B. , Livingstone W. , Murphy C. , Hodgson A. , Rafferty M. , Smith OP An open-label study of the role of adjuvant hemostatic support with protein C replacement therapy in purpura fulminans-associated meningococcemia. Blood 2000; 96: 3719—3724.

447.

Garber K. Protein C may be sepsis solution. N Engl J Med 2001; 344: 699—709.

448.

Marlar RA, Endres , Brooks J. , Miller C. Serial studies of protein C and its plasma inhibitor in patients with disseminated intravascular coagulation. Blood 1985; 66: 59—63.

449.

Fisher Jr CJ , Yan SB Protein C levels as a prognostic indicator of outcome in sepsis and related diseases. Crit Care Med 2000; 28 (Suppl. 9): S49—S56.

450.

ten Cate H. Pathophysiology of disseminated intravascular coagulation in sepsis. Crit Care Med 2000; 28 (Suppl. 9): S9—S11.

451.

Powars D. , Larsen R. , Johnson J. et al. Epidemic meningococcemia and purpura fulminans with induced protein C deficiency. Clin Infect Dis 1993 ; 17: 254—261.

452.

Fijnvandraat K. , Derkx B. , Peters M. et al. Coagulation activation and tissue necrosis in meningococcal septic shock: severely reduced protein C levels predict a high mortality. Thromb Haemost 1995; 73: 15—20.

453.

Mesters RM , Helterbrand J. , Utterback BG et al. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications. Crit Care Med 2000; 28: 2209—2216.

454.

Esmon CT Regulation of blood coagulation. Biochim Biophys Acta 2000; 1477: 349—360.

455.

Esmon CT , Fukudome K. , Mather T. et al. Inflammation, sepsis, and coagulation. Haematologica 1999; 84: 254—259.

456.

Nakatsuka M. , Kumazawa Y. , Ikeda S. et al. Antitumor and antimicrobial activities of lipid A-subunit analogue GLA-27. J Clin Lab Immunol 1988; 26: 43—47.

457.

Kornbluth RS , Oh PS , Munis JR , Cleveland PH , Richman DD Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro. J Exp Med 1989; 169: 1137—1151.

458.

Gessani S. , Testa U. , Varano B. et al. Enhanced production of LPS-induced cytokines during differentiation of human monocytes to macrophages. Role of LPS receptors. J Immunol 1993; 151: 3758—3766.

459.

Zhang M. , Tracey KJ Endotoxin and cancer. In: Brade H , Opal SM , Vogel SN , Morrisson DC. (eds) Endotoxin in Health and Disease, New York: Marcel Dekker , 1999; 915—926.

460.

Ulrich JT , Myers KR Monophosphoryl lipid A as an adjuvant. Past experiences and new directions . Pharm Biotechnol 1995; 6: 495—524.

461.

Baldridge JR , Crane RT Monophosphoryl lipid A (MPL) formulations for the next generation of vaccines . Methods 1999; 19: 103—107.

462.

De Becker G , Moulin V. , Pajak B. et al. The adjuvant monophosphoryl lipid A increases the function of antigen-presenting cells. Int Immunol 2000; 12: 807—815.

463.

Gereda JE , Leung DY , Thatayatikom A. et al. Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma . Lancet 2000; 355: 1680—1683.

464.

Harris DT , Matyas GR , Gomella LG et al. Immunologic approaches to the treatment of prostate cancer. Semin Oncol 1999; 26: 439—447.

465.

Ribi E. , Cantrell JL , Takayama K. , Qureshi N. , Peterson J. , Ribi HO Lipid A and immunotherapy. Rev Infect Dis 1984; 6: 567—572.

466.

Manthey CL , Perera PY , Salkowski CA , Vogel SN Taxol provides a second signal for murine macrophage tumoricidal activity. J Immunol 1994; 152: 825—831.

467.

Chapoval AI , Tamada K. , Chen L. In vitro growth inhibition of a broad spectrum of tumor cell lines by activated human dendritic cells. Blood 2000; 95: 2346—2351.

468.

Engelhardt R. , Mackensen A. , Galanos C. Phase I trial of intravenously administered endotoxin (Salmonella abortus equi) in cancer patients. Cancer Res 1991; 51: 2524—2530.

469.

Goto S. , Sakai S. , Kera J. , Suma Y. , Soma GI , Takeuchi S. Intradermal administration of lipopolysaccharide in treatment of human cancer . Cancer Immunol Immunother 1996; 42: 255—261.