ATTENUATION OF INTERLEUKIN-8 EXPRESSION IN C6-DEFICIENT RABBITS AFTERMYOCARDIAL ISCHEMIA REPERFUSION/

Neutrophil accumulation and activation of the complement system with s ubsequent deposition of the cytolytic membrane attack complex (MAC) ha ve been implicated in the pathogenesis of myocardial ischemia/reperfus ion injury. The MAC, when present in high concentrations, promotes tar get cell lysis. However, relatively little is known about the potentia l modulatory role of sublytic concentrations of the MAC on nucleated c ell function in vivo. In vitro studies demonstrated that the MAC regul ates cell function by promoting the expression of pro-inflammatory med iators, including adhesion molecules and pro-inflammatory cytokines. W e examined, using C6-deficient and CG-sufficient rabbits, the regulato ry role of the MAC in mediating IL-8 expression and subsequent neutrop hil recruitment in the setting of myocardial ischemia/reperfusion inju ry. CG-deficient and CG-sufficient rabbits were subjected to 30 min of regional myocardial ischemia followed by a period of reperfusion. In addition to a significant reduction in myocardial infarct size in CG-d eficient animals, analysis of myocardial tissue demonstrated a decreas e in neutrophil influx into the infarcted region. The reduction in neu trophil influx correlated with the decreased expression of the neutrop hil chemotactic cytokine IL-8, as determined by ELISA and immunohistoc hemical analysis, The results derived from this study provide evidence that the MAC has an important function in mediating the recruitment o f neutrophils to the reperfused myocardium (C) 1998 Academic Press Lim ited.