Sublytic complement attack reduces infarct size in rabbit isolated hearts: evidence for C5a-mediated cardioprotection.
Sublytic complement attack can elicit protective cellular responses without precipitating cell death. Our investigation examined the effects of non-lethal complement activation in isolated hearts. New Zealand white rabbit hearts were subjected to 30 min of ischemia followed by 1 h of reperfusion. Prior to ischemia, hearts were perfused for 20 min with 0.5% normal human plasma (NHP). Hearts treated with NHP developed significantly (p<0.05) smaller infarcts compared with controls, expressed as percent of area at risk (AAR) (25.3+/-4.0% vs. 40.9+/-4.3%, respectively). Heat-inactivation, soluble complement receptor 1 (sCR1; 20 nM), and anti-C5a antibody reversed the protective effect of NHP (39.0+/-3.1%, 41.7+/-5.1% and 38.4+/-2.3% AAR, respectively). Hearts treated with 3 nM C5a exhibited infarct sizes similar to those exposed to NHP (27.6+/-5.0% AAR). sCR1 alone did not affect infarct size (37.9+/-4.5% AAR). The results suggest that non-lethal complement activation attenuates reperfusion injury through formation of C5a.
Tanhehco
E J
EJ
Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, A220C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0632, USA.
Lee
H
H
Lucchesi
B R
BR
D000818:Animals; D003167:Complement Activation / Q000276:immunology*; D015936:Complement C5a / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D006439:Hemodynamics / Q000276:immunology; D006461:Hemolysis / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D011817:Rabbits; D017463:Receptors, Complement 3b / Q000502:physiology; D012995:Solubility
D015938:Complement Membrane Attack Complex; D017463:Receptors, Complement 3b; D015936:Complement C5a