PLATELET PARTICIPATION IN LIVER-INJURY FROM GRAM-NEGATIVE BACTERIAL LIPOPOLYSACCHARIDE IN THE RAT

Intravenous administration of lipopolysaccharide (LPS) to rats results in multifocal, primarily midzonal hepatic necrosis. The hepatic injur y is associated with inflammation and is dependent on neutrophils and the coagulation system. After LPS injection into rats, plasma fibrinog en concentration and numbers of blood platelets and leukocytes decreas e. Results of our studies, using immunocytochemistry for the detection of neutrophils and (111)indium-labeling to identify platelets, indica te that both neutrophils and platelets accumulate within the liver ear ly after administration of LPS to rats. The accumulation of platelets in the liver before the onset of injury suggested that platelets contr ibute to the manifestation of LPS-induced hepatotoxicity. To test this hypothesis, the number of circulating blood platelets was decreased b y the administration of an anti-rat platelet serum (APS) before LPS ad ministration. The consequent thrombocytopenia by APS administration wa s associated with an attenuation of both LPS-induced liver injury and the activation of the coagulation system. However, the APS treatment d id not prevent the hepatic neutrophil accumulation. These results sugg est that platelets contribute to the pathogenesis of liver injury afte r LPS administration, perhaps through their integral role in coagulati on and/or interaction with neutrophils, but they do not appear to cont ribute to hepatic neutrophil accumulation.