Endothelial injury induced by bacterial endotoxin: effect of complement depletion

The role of complement activation in the pathogenesis of endothelial injury caused by bacterial endotoxin was investigated in the rat. DNA synthesis in aortic endothelium was compared 48 hours after an intravenous injection of endotoxin (50 - 500 mug) in normal rats and in rats depleted of haemolytic complement by purified cobra venom factor. At the time of endotoxin administration the rats treated with cobra venom factor had less than 3% of the normal haemolytic complement level, their fibrinogen level was increased and clot retraction was impaired. Endotoxin stimulated endothelial DNA synthesis to the same degree in normal and in complement-depleted rats. Cobra venom factor alone did not stimulate endothelial DNA synthesis. The complement-depleted rats given 500 mug endotoxin were less thrombocytopenic than normal rats at the time of sacrifice, but the difference was not statistically significant. We conclude that the injurious effect endotoxin has on endothelium is not mediated by activation of late components of complement.