The severity of ischaemic heart disease is markedly enhanced in type 2 diabetes.We recently reported that complement activation exacerbates I/R injury in the type 2 diabetic heart.The purpose of this study was to isolate and examine MBL pathway activation following I/R injury in the diabetic heart. ZLC and ZDF rats underwent 30 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion.Two different groups of ZDF rats were treated with either FUT-175, a broad complement inhibitor, or P2D5, a monoclonal antibody raised against rat MBL-A. ZDF rats treated with FUT175 and P2D5 had significantly decreased myocardial infarct size, C3 deposition and neutrophil accumulation compared with untreated ZDF controls.Taken together, these findings indicate that the MBL pathway plays a key role in the severity of complement-mediated I/R injury in the type 2 diabetic heart.
Zhang, L., Zalewsk,i A, Liu, Y. (2003) Diabetes-induced oxidative stress and low-grade inflammation in porcine coronary arteries. Circulation108: 472-8.
2.
Stockklauser-Farber, K., Ballausen, T., Laufer , A., Rosen, P. (2000) Influence of diabetes on cardiac nitric oxide synthase expression and activity . Biochim Biophys Acta1535: 10-20.
3.
Tuttle, HA, Davis-Gorman, G., Goldman, S., Copeland, JG, McDonagh, PF (2004) Proinflammatory cytokines are increased in type 2 diabetic women with cardiovascular disease. J Diabetes Complicat18: 343-51.
4.
Jordan, JE, Montalto, MC, Stahl, GL (2001) Inhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury. Circulation104: 1413-8.
5.
Collard, CD, Väkevä, A., Morrissey, MA, et al. (2000) Complement activation after oxidative stress. Role of the lectin complement pathway. Am J Pathol156: 1549-56.
6.
La Bonte, LR , Davis-Gorman, G., Stahl , GL, McDonagh, PF (2008) Complement inhibition reduces injury in the type 2 diabetic heart following ischaemia and reperfusion . Am J Physol Heart Circ Physiol294: H1282-90.
7.
Pinckard, RN , O'Rourke, RA, Crawford , MH, et al. (1980) Complement localization and mediation of ischemic injury in baboon myocardium . J Clin Invest66: 1050-6.
8.
Vakeva, A., Laurila, P., Meri, S. (1992) Loss of expression of protectin (CD59) is associated with complement membrane attack complex deposition in myocardial infarction . Lab Invest67: 608-16.
9.
Hokama, JY, Ritter, LS, Davis-Gorman, G., Cimetta, AD, Copeland, JG, McDonagh, PF (2000) Diabetes enhances leukocyte accumulation in the coronary microcirculation early in reperfusion following ischaemia. J Diabetes Complicat14: 96-107.
10.
Ritter, LS, McDonagh, PF (1997) Low flow reperfusion after myocardial ischaemia enhances leukocyte accumulation in coronary microcirculation. Am J Physiol273: H1154-65.
11.
Tonnesen, MG , Anderson, DC, Springer , TA (1989) Adherence of neutrophils to cultured human microvascular endothelial cells. Stimulation by chemotactic peptides and lipid mediators and dependence upon the Mac-1, LFA-1, p150.95 glycoprotein family. J Clin Invest83: 637-46.
12.
Sacks, T., Moldow, CF, Craddock, PR, Bowers, TK, Jacob, HS (1978) Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes: An in vitro model of immune vascular damage. J Clin Invest61: 1161-67.
13.
Saddi, S., Holzknecht, RA, Patte, CP (2000) Endothelial cell activation by pore-forming structures: Pivotal role for Interleukin-1á. Circulation101: 1867-73.
14.
Kilgore, KS , Flory, CM, Miller , BP (1996) The membrane attack complex of complement induces interleukin-8 and monocyte chemoattractant protein-1 secretion from human umbilical vein endothelial cells. Am J Pathol149: 953-61.
15.
Walsh, M., Bourcier, T., Takahashi, K., et al. (2005) Mannose binding lectin is a regulator of inflammation that accompanies myocardial ischaemia and reperfusion injury . J Immunol175: 541-46.
16.
Hansen, T., Tarnow, L., Thiel, S., et al. (2004) Association between mannose-binding lectin and vascular complications in type 1 diabetes. Diabetes53: 1570-76.
17.
Clark, JB, Palmer, CJ, Shaw, WN (1983) The diabetic Zucker Fatty Rat (41611). Proc Soc Exp Biol Med173: 68-75.
18.
Fujii, S., Hitomi, Y. (1981) New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. Biochim Biophys Acta661: 342-45.
19.
Ikari, N., Sakai, Y., Hitomi, Y., Fujii, S. (1983) New synthetic inhibitor to the alternative complement pathway. Immunology49: 685.
20.
Walsh, MC, Shaffer, LA, Guikema, BJ, et al. (2007) Fluorochrome-linked immunoassay for functional analysis of the mannose binding lectin complement pathway to the level of C3 cleavage. J Immuno Methods323: 147-59.
21.
Pfeifer, PH , Kawahara, MS, Hugli , TE (1999) Possible mechanism for in vitro complement activation in blood and plasma samples: Futhan/EDTA controls in vitro complement activation. Clin Chem45: 1190-99.
22.
Homeister, JW, Satoh, P., Lucchesi , BR (1992) Effects of complement activation in the isolated heart. Role of the terminal complement components . Circ Res71: 303-19.
23.
Kubota, K., Mizoguchi, H., Miura, Y., Suda, T., Takaku, F. (1980) A new technique for the cytochemical examination of human hemopoietic cells grown in agar gel. Exp Hematol8: 339-44.
24.
Lefer, AM, Weyrich, A., Buerke, M. (1994) Role of selectins, a new family of adhesion molecules, in ischaemia-reperfusion injury. Cardiovasc Res28: 289-94.
25.
Vakeva, AP, Agah, A., Rollins, SA, Matis, LA, Li, L., Stahl, GL (1998) Myocardial infarction and apoptosis after myocardial ischaemia and reperfusion. Role of the terminal complement components and inhibition by anti-C5 therapy. Circulation97: 2259-67.
26.
American Heart Association. ( 2005) Heart disease and stroke statistics - 2005 update.
27.
Kannel, WB, McGee, DL (1979) Diabetes and cardiovascular disease: the Framingham study. JAMA241: 2035-38.
28.
stergaard, J., Hansen, TK, Thiel , S., Flyvbjerg, A. (2005) Complement activation and diabetic vascular complications. Clin Chim Acta361: 10-19.
29.
Jerath, RS, Burek, CL, Hoffman, WH, Passmore, GG (2005) Complement activation in diabetic ketoacidosis and its treatment. Clin Immunol116: 11-17.
30.
Scantlebury, T., Sniderman, AD, Cianflone , K. (2001) Regulation by retinoic acid of acylation-stimulating protein and complement C3 in human adipocytes . Biochem J356: 445-52.
31.
Scantlebury, T., Maslowska, M., Cianflone , K. (1998) Chylomicron-specific enhancement of acylation stimulating protein and precursor protein C3 production in differentiated human adipocytes. J Biol Chem273: 20903-09.
32.
Muscari, A. , Massarelli, G., Bastagli , L., et al. (2000) Relationship of serum C3 to fasting insulin, risk factors and previous ischaemic events in middle-aged men. Eur Heart J21: 1081-90.
33.
Hansen, TK, Thiel, S., Wouters, PJ, Christiansen, JS, Van den Berghe, G. (2003) Intensive insulin therapy exerts antiinflammatory effects in critically ill patients and counteracts the adverse effect of low mannose-binding lectin levels. J Clin Endocrinol Metab88: 1082-88.
34.
Engstrom, G. , Hedblad, B., Eriksson, KF, Janzon, L., Lindgarde, F. (2005) Complement C3 is a risk factor for the development of diabetes: a population-based cohort study. Diabetes54: 570-76.
35.
McMillan, DE (1980) Elevation of complement components in diabetes mellitus. Diabetes Metab6: 265-70.
36.
Busche, MN, Walsh, MC, McMullen, ME, Guikema, BJ, Stahl, GL (2008) Mannose-binding lectin plays a critical role in myocardial ischaemia and reperfusion injury in a mouse model of diabetes. Diabetologia51: 1544-51.
37.
Henry, ML, Davidson, LB, Wilson, JE, et al. (2008) Whole blood aggregation and coagulation in db/db and ob/ob mouse models of type 2 diabetes. Blood Coagul Fibrinolysis19: 124-34.
38.
Paul, W., Queen, LR, Page, CP, Ferro, A. (2007) Increased platelet aggregation in vivo in the Zucker Diabetic Fatty rat: differences from the streptozotocin diabetic rat. Br J Pharmacol150: 105-11.
39.
Fiane, AE, Videm, V., Lingaas, PS, et al. (2003) Mechanism of complement activation and its role in the inflammatory response after thoracoabdominal aortic aneurysm repair . Circulation108: 849-56.
de Vries, B. , Kohl, J., Leclercq , WKG, et al. (2003) Complement factor C5a mediates renal ischaemia-reperfusion injury independent from neutrophils . J Immunol170: 3883-89.
42.
Acosta, J., Hettinga, J., Flückiger, R., et al. (2000) Molecular basis for a link between complement and the vascular complications of diabetes. PNAS97: 5450-55.
43.
Ito, W. , Schäfer, JJ, Bhakdi , S., et al. (1996) Influence of the terminal complement-complex on reperfusion injury, no-reflow and arrhythmias: a comparison between C6-competent and C6-deficient rabbits . Cardiovasc Res32: 294-305.
44.
Rossen, RD, Swain, JL, Michael, LH, Weakley, S., Giannini, E., Entman, ML (1985) Selective accumulation of the first component of complement and leukocytes in ischemic canine heart muscle. A possible initiator of an extra myocardial mechanism of ischemic injury. Circ Res57: 119-30.
45.
Dreyer, WJ, Michael, LH, West, S., et al. (1991) Neutrophil accumulation in ischemic canine myocardium. Insights into time course, distribution, and mechanism of localization during early reperfusion. Circulation84: 400-11.
46.
Akatsu, H., Abe, M., Miwa, T., et al. (2002) Distribution of rat C5a anaphylatoxin receptor . Microbiol Immunol46: 863-74.
Atsuumi, T. , Yaoita, H., Shichishima , T., Maehara, K., Fujita, T., Maruyama, Y. (2001) Complement and polymorphonuclear leukocyte activation each play a role in determining myocardial ischaemia-reperfusion injury. Jpn Circ J65: 659-66.
49.
Simpson, PJ , Todd III, RF, Fantone , JC, Mickelson, JR, Griffin, JD, Lucchesi, BR (1988) Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mol, Anti-CD11b) that inhibits leukocyte adhesion. J Clin Invest81: 624-29.
50.
McDonagh, PF , Hokama, JY, Copeland , JG, Reynolds, JM (1997) The blood contribution to early myocardial reperfusion injury is amplified in diabetes. Diabetes46: 1859-67.
51.
Ritter, LS, Orozco, JA, Coull, BM, McDonagh, PF (2000) Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation during early reperfusion after stroke. Stroke31: 1153-61.
52.
Soriano, SG , Coxon, A., Wang , YF, et al. (1999) Mice deficient in Mac-1 (CD11b/CD18) are less susceptible to cerebral ischaemia/reperfusion injury. Stroke30: 134-39.
53.
Rinder, CS, Fontes, M., Mathew, JP, Rinder, HM, Smith, BR, Multicenter Study of Perioperative Ischaemia (McSPI) Research Group. (2003) Neutrophil CD11b upregulation during cardiopulmonary bypass is associated with postoperative renal injury . Ann Thorac Surg75: 899-905.
54.
Booth, G., Stalker, TJ, Lefer, AM, Scalia, R. (2001) Elevated ambient glucose induces acute inflammatory events in the microvasculature: effects of insulin. Am J Physiol Endocrinol Metab280: E848-56.
55.
Merin, M. (2008) Global Health: addressing the world's health challenges. Diabetes threatens lives worldwide. [Web Page]; http://www.america.gov/st/health-english/2008/April/20080410113749liameruoy0.5424921.html .
