EFFECT OF SUPERNATANTS FROM KUPFFER CELLS STIMULATED WITH GALACTOSAMINE AND ENDOTOXIN ON THE FUNCTION OF ISOLATED RAT HEPATOCYTES

Activated Kupffer cells may release substances that are involved in li ver injury induced by galactosamine and endotoxin. In the present stud y Kupffer cells were isolated from rat livers, cultured for 24 hours a nd incubated with galactosamine, endotoxin (LPS) or tumor necrosis fac tor-alpha for 4 or 24 hours. The Kupffer cell-conditioned media were t hen added in separate experiments to freshly prepared isolated rat hep atocytes to determine their cytotoxic effect. No significant effects o n the rate of protein synthesis, as assessed by the incorporation of C -14-leucine on lactate dehydrogenase enzyme release from hepatocytes d uring 1 h incubation was found as compared with conditioned media from control Kupffer cells. In further experiments, Kupffer cells incubate d for 4 hours with LPS and galactosamine were shown to produce thrombo xane B2 and also the potentially cytoprotective prostaglandins PGE2 an d small amounts of prostacyclin measured as 6-keto-PGF1alpha. It is co ncluded that under the conditions of the present experiments, factors secreted by cultured Kupffer cells have no cytotoxic effects on isolat ed rat hepatocytes during short-term incubation.