SYNERGISTIC ACTION OF HEPATOCYTE MEMBRANE DEFECT AND ACTIVATED COMPLEMENT-SYSTEM IN LIVER-CELL DEATH - EXPERIMENTAL APPROACH TO FULMINANT HEPATIC-FAILURE
The possibility that a membrane defect of hepatocytes activates the complement [C] system which leads to massive liver cell necrosis was studied. Low doses of galactosamine (50, 100 and 200 mg/kg) were administered to rats with and without an additional i.v. injection of sublethal doses of endotoxin (1.5 mg/kg). The latter was done to activate the C system via the C3[3rd component of complement]-bypath. After 50 mg/kg and 100 mg/kg or an additional administration of endotoxin liver cell necrosis was not observed. A dose of 200 mg/kg led to moderate liver cell necrosis, and when administered with endotoxin fulminant hepatic necrosis developed. The explanation was given that only after 200 mg/kg were alterations of hepatocytes membranes present, which prepare liver cells for complement mediated hepatocytolysis. In rats given 1 g/kg galactosamine in addition to endotoxin it was demonstrated by immunohistology that the C3 was already fixed on hepatocyte plasma membranes at 3 h and was accumulated within areas of necrotic liver parenchymal cells at 12 h. Liver cell death is suggested as complement mediated if the membranes are altered. Clinical implications in terms of fulminant hepatic failure and an approach to effective treatment regimens are given.