RENAL MICROVASCULAR INJURY-INDUCED BY ANTIBODY TO GLOMERULAR ENDOTHELIAL-CELLS IS MEDIATED BY C5B-9

We have recently developed a model of thrombotic microangiopathy with injury to the glomerular endothelial cell (GEN) induced by heterologou s antibody to rat GEN. In addition to GEN injury rats developed glomer ular platelet aggregation and fibrin deposition, acute renal failure, and acute tubular necrosis with interstitial inflammation. To study th e role of complement in mediating this lesion, we induced the disease in normal complement PVG rats and measured the effects of generalized complement depletion with cobra venom factor (CVF) and of selective C6 deficiency using genetically C6 deficient PVG animals. Complement suf ficient rats developed severe endothelial injury accompanied by platel et aggregation, fibrin deposition, decrease in endothelial cells asses sed by antibody staining in the glomerulus, and macrophage infiltratio n. These changes were associated with marked reduction in renal functi on. These features were either absent or markedly diminished in comple ment depleted or C6 deficient rats. This demonstrates that C5b-9, the terminal product of activation of the complement cascade, plays an imp ortant role in the pathogenesis of this immune renal microvascular end othelial injury model. Thus, the complement system may play a pathogen ic role in renal microvascular diseases such as thrombotic microangiop athy.