REPERFUSION INJURY OF ISCHEMIC SKELETAL-MUSCLE IS MEDIATED BY NATURALANTIBODY AND COMPLEMENT

Reperfusion of ischemic tissue induces an acute inflammatory response that can result in necrosis and irreversible cell injury to both local vascular endothelium and parenchyma. To examine the pathogenesis of i schemia/reperfusion injury, we have used mice deficient in complement components C3, C4, or serum immunoglobulin in a hindlimb model of isch emia. We found that mice homozygous deficient in C3 or C4 were equally protected against reperfusion injury based on a significant reduction in leakage of radiolabeled albumin out of the vasculature. This demon strates that classical pathway complement is an important factor in th e initiation of inflammation following reperfusion. Furthermore, mice deficient in serum immunoglobulin were equally protected and this prot ection could be reversed by reconstitution with serum from normal mice . Thus, this report describes a novel mechanism for reperfusion injury that involves antibody deposition and activation of complement leadin g to inflammation permeability.