Surfactant protein-A enhances ureaplasmacidal activity in vitro

Abstract

Background: Persistent respiratory tract colonization with Ureaplasma spp. in preterm infants is a significant risk factor for the development of the chronic lung disorder, bronchopulmonary dysplasia (BPD). Surfactant protein-A (SP-A), a lung collectin critical for bacterial clearance and regulating inflammation, is deficient in the preterm lung. In an experimental Ureaplasma-pneumonia model, infected SP-A deficient mice exhibited delayed bacterial clearance and an exaggerated inflammatory response compared to infected wild-type mice. The objective was to analyze the role of SP-A in Ureaplasma clearance in vitro.

Subjects and Methods: We analyzed SP-A binding to Ureaplasma isolates and SP-A-mediated ureaplasmal phagocytosis and killing by cultured RAW 264.7 macrophages.

Results: Calcium-dependent SP-A binding was similar among Ureaplasma isolates tested. Pre-incubation of RAW 264.7 cells with SP-A (10-50 μg/ml) enhanced phagocytosis of fluorescein-isothiocyanate (FITC)-labeled Ureaplasma. Surfactant protein-A also increased ureaplasmacidal activity of RAW 264.7 cells by 2.1-fold over 4 h. Pre-incubation of RAW 264.7 cells with 10 μg/ml SP-A reduced lipopolysaccharide (LPS) (100 ng/ml) and Ureaplasma (10⁶ color changing units/ml)-stimulated release of tumor necrosis factor-α (TNF-α) by 46% and 43%, respectively, but did not affect transforming growth factor β₁ (TGFβ₁) release.

Conclusions: These in vitro data confirm that SP-A is important in host defense to perinatally-acquired Ureaplasma infection.

Keywords

Surfactant protein A Ureaplasma parvum Ureaplasma urealyticum bronchopulmonary dysplasia

References

Volgmann T. , Ohlinger R. , Panzig B. Ureaplasma urealyticum - harmless commensal or underestimated enemy of human reproduction? A review. Arch Gynecol Obstet 2005; 273: 133-139.

Waites KB , Katz B. , Schelonka RL Mycoplasmas and ureaplasmas as neonatal pathogens. Clin Microbiol Rev 2005; 18: 757-789.

Castro-Alcaraz S. , Greenberg EM , Bateman DA , Regan JA Patterns of colonization with Ureaplasma urealyticum during neonatal intensive care unit hospitalizations of very low birth weight infants and the development of chronic lung disease . Pediatrics 2002; 110: E45.

Schelonka RL , Katz B. , Waites KB , Benjamin Jr DK Critical appraisal of the role of Ureaplasma in the development of bronchopulmonary dysplasia with metaanalytic techniques . Pediatr Infect Dis J 2005; 24: 1033-1039.

Jobe AH , Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163: 1723-1729.

Jobe AH , Ikegami M. Antenatal infection/inflammation and postnatal lung maturation and injury . Respir Res 2001; 2: 27-32.

Patterson AM , Taciak V. , Lovchik J. , Fox RE , Campbell AB , Viscardi RM Ureaplasma urealyticum respiratory tract colonization is associated with an increase in IL-1β and TNF-α relative to IL-6 in tracheal aspirates of preterm infants. Pediatr Infect Dis J 1998; 17: 321-328.

Viscardi RM , Manimtim WM , Sun CCJ , Duffy L. , Cassell GH Lung pathology in premature infants with Ureaplasma urealyticum infection . Pediatr Dev Pathol 2002; 5: 141-150.

Viscardi R. , Manimtim W. , He JR et al. Disordered pulmonary myofibroblast distribution and elastin expression in preterm infants with Ureaplasma urealyticum pneumonitis. Pediatr Dev Pathol 2006; 9: 143-151.

10.

Viscardi RM , Kaplan J. , Lovchik JC et al. Characterization of a murine model of Ureaplasma urealyticum pneumonia. Infect Immun 2002; 70: 5721-5729.

11.

Yoder BA , Coalson JJ , Winter VT , Siler-Khodr T. , Duffy LB , Cassell GH Effects of antenatal colonization with Ureaplasma urealyticum on pulmonary disease in the immature baboon. Pediatr Res 2003; 54: 797-807.

12.

Viscardi RM , Atamas SP , Luzina IG et al. Antenatal Ureaplasma urealyticum respiratory tract infection stimulates proinflammatory, profibrotic responses in the preterm baboon lung. Pediatr Res 2006; 60: 141-146.

13.

Moss TJ , Nitsos I. , Ikegami M. , Jobe AH , Newnham JP Experimental intrauterine Ureaplasma infection in sheep. Am J Obstet Gynecol 2005; 192: 1179-1186.

14.

Moss TJ , Knox CL , Kallapur SG et al. Experimental amniotic fluid infection in sheep: effects of Ureaplasma parvum serovars 3 and 6 on preterm or term fetal sheep. Am J Obstet Gynecol 2008; 198: 122 e121-128.

15.

Manimtim WM , Hasday JD , Hester L. , Fairchild KD , Lovchik JC , Viscardi RM Ureaplasma urealyticum modulates endotoxin-induced cytokine release by human monocytes derived from preterm and term newborns and adults. Infect Immun 2001; 69: 3906-3915.

16.

Wright JR , Borron P. , Brinker KG , Folz RJ Surfactant protein A: regulation of innate and adaptive immune responses in lung inflammation. Am J Respir Cell Mol Biol 2001; 24: 513-517.

17.

LeVine AM , Kurak KE , Wright JR et al. Surfactant protein-A binds group B streptococcus enhancing phagocytosis and clearance from lungs of surfactant protein-A-deficient mice. Am J Respir Cell Mol Biol 1999; 20: 279-286.

18.

Hickman-Davis JM , Gibbs-Erwin J. , Lindsey JR , Matalon S. Role of surfactant protein-A in nitric oxide production and mycoplasma killing in congenic C57BL/6 mice. Am J Respir Cell Mol Biol 2004; 30: 319-325.

19.

Harrod KS , Trapnell BC , Otake K. , Korfhagen TR , Whitsett JA SP-A enhances viral clearance and inhibits inflammation after pulmonary adenoviral infection. Am J Physiol 1999; 277: L580-L588.

20.

LeVine AM , Hartshorn K. , Elliott J. , Whitsett J. , Korfhagen T. Absence of SP-A modulates innate and adaptive defense responses to pulmonary influenza infection. Am J Physiol 2002; 282: L563-L572.

21.

Borron P. , McIntosh JC , Korfhagen TR , Whitsett JA , Taylor J. , Wright JR Surfactant-associated protein A inhibits LPS-induced cytokine and nitric oxide production in vivo. Am J Physiol 2000; 278: L840-L847.

22.

Ballard PL , Hawgood S. , Liley H. et al. Regulation of pulmonary surfactant apoprotein SP 28-36 gene in fetal human lung. Proc Natl Acad Sci USA 1986 ; 83: 9527-9531.

23.

Whitsett JA , Pilot T. , Clark JC , Weaver TE Induction of surfactant protein in fetal lung. Effects of cAMP and dexamethasone on SAP-35 RNA and synthesis. J Biol Chem 1987; 262: 5256-5261.

24.

Miyamura K. , Malhotra R. , Hoppe HJ et al. Surfactant proteins A (SP-A) and D (SP-D): levels in human amniotic fluid and localization in the fetal membranes . Biochim Biophys Acta 1994; 1210: 303-307.

25.

Awasthi S. , Coalson JJ , Crouch E. , Yang F. , King RJ Surfactant proteins A and D in premature baboons with chronic lung injury (bronchopulmonary dysplasia). Evidence for an inhibition of secretion . Am J Respir Crit Care Med 1999; 160: 942-949.

26.

Hallman M. , Merritt TA , Akino T. , Bry K. Surfactant protein A, phosphatidylcholine, and surfactant inhibitors in epithelial lining fluid. Correlation with surface activity, severity of respiratory distress syndrome, and outcome in small premature infants. Am Rev Respir Dis 1991; 144: 1376-1384.

27.

Famuyide ME , Hasday JD , Carter HC , Chesko KL , He JR , Viscardi RM Surfactant protein-A limits Ureaplasma-mediated lung inflammation in a murine pneumonia model. Pediatr Res 2009; 66: 162-167.

28.

Huang W. , Wang G. , Phelps DS , Al-Mondhiry H. , Floros J. Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells: effect of ozone-induced SP-A oxidation. Am J Physiol 2004; 286: L546-L553.

29.

Ding J. , Umstead TM , Floros J. , Phelps DS Factors affecting SP-A-mediated phagocytosis in human monocytic cell lines . Respir Med 2004; 98: 637-650.

30.

Smith DGE , Russell WC , Thirkell D. Adherence of Ureaplasma urealyticum to human epithelial cells. Microbiology 1994; 140: 2893-2898.

31.

Piboonpocanun S. , Chiba H. , Mitsuzawa H. et al. Surfactant protein A binds Mycoplasma pneumoniae with high affinity and attenuates its growth by recognition of disaturated phosphatidyl-glycerols. J Biol Chem 2005; 280: 9-17.

32.

Hickman-Davis JM , Lindsey JR , Zhu S. , Matalon S. Surfactant protein A mediates mycoplasmacidal activity of alveolar macrophages. Am J Physiol 1998; 274: L270-L277.

33.

Chiba H. , Pattanajitvilai S. , Mitsuzawa H. , Kuroki Y. , Evans A. , Voelker DR Pulmonary surfactant proteins A and D recognize lipid ligands on Mycoplasma pneumoniae and markedly augment the innate immune response to the organism . Chest 2003; 123: 426S.

34.

Gardai SJ , Xiao Y. , Dickinson M. , Nick JA , Voelker DR , Greene KE By binding SIRPα or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell 2003; 115: 13-23.

35.

Minoo P. , Segura L. , Coalson JJ , King RJ , DeLemos RA Alterations in surfactant protein gene expression associated with premature birth and exposure to hyperoxia. Am J Physiol 1991; 261: L386-L392.

36.

Stevens PA , Schadow B. , Bartholain S. , Segerer H. , Obladen M. Surfactant protein A in the course of respiratory distress syndrome . Eur J Pediatr 1992; 151: 596-600.