Complement activation and inhibition in myocardial ischemia and reperfusion injury.
The myocardial inflammatory response that occurs as a result of ischemia and reperfusion is similar to that which occurs in other tissues. Activation of the complement system is an integral part of the initiation and maintenance of any inflammatory response. It and other immune system mediators participate in the promotion of neutrophil adherence to endothelium by modulating expression of various adhesion molecules. The complement system also serves an integral role in mediating neutrophil activation, the results of which have been documented in the setting of myocardial ischemia and reperfusion. Another aspect of the complement cascade, which has received little attention with respect to the heart, is the direct effects of complement activation such as endothelial and myocardial cell cytotoxicity mediated by the membrane attack complex. It is likely that this form of tissue injury contributes significantly to myocardial reperfusion injury. Given the numerous contributions of the complement system to the generation of the inflammatory response, and to directly-mediated tissue injury, selective inhibitors of the complement system have great potential to limit reperfusion injury. This has already been demonstrated for the complement inhibitor sCR1. In the future, it is likely that any therapeutic treatment of reperfusion injury will include modulation of the effects of complement activation.
Homeister
J W
JW
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0626.
Lucchesi
B R
BR
D000818:Animals; D003167:Complement Activation / Q000502:physiology*; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D003165:Complement System Proteins / Q000502:physiology*; D006801:Humans; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology
D003169:Complement Inactivator Proteins; D003165:Complement System Proteins