ROLE OF PLATELET-ACTIVATING-FACTOR IN PATHOGENESIS OF GALACTOSAMINE-LIPOPOLYSACCHARIDE-INDUCED LIVER-INJURY

In an attempt to clarify the role of platelet-activating factor (PAF) in the pathogenesis of hepatic injury induced by galactosamine (GalN) plus lipopolysaccharide (LPS), effects of WEB 2086 (PAF receptor antag onist) on hepatic injury in vivo as well as on neutrophil adherence to hepatic endothelial cells in vitro have been investigated, as we have recently clarified the role of neutrophils in this experimental model of hepatic injury, Although an enhanced serum TNF-alpha level after G alN-LPS administration was not reduced by WEB 2086, hepatic injury and hepatic neutrophil accumulation in the liver after GalN-LPS administr ation were attenuated by WEB 2086, An in vitro study revealed that an enhanced neutrophil adhesion to hepatic endothelial cells by stimulati on with the sera that were collected from the GalN-LPS-treated rats, w as reduced in the presence of WEB 2086 in a dose-dependent manner. In addition, LPS, TNF-alpha, and PAF were found to enhance the neutrophil adherence to hepatic endothelial cells, which was reduced in the pres ence of WEB 2086. These results suggest that PAF play an important rol e in the GalN-LPS induced hepatic injury and that PAF receptor antagon ist reduces the neutrophil adherence to hepatic endothelial cells in t he liver.