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 injury is associated with inflammation and is dependent on neutrophils and the coagulation system. After LPS injection into rats, plasma fibrinogen concentration and numbers of blood platelets and leukocytes decrease. Results of our studies, using immunocytochemistry for the detection of neutrophils and 111indium-labeling to identify platelets, indicate that both neutrophils and platelets accumulate within the liver early after administration of LPS to rats. The accumulation of platelets in the liver before the onset of injury suggested that platelets contribute to the manifestation of LPS-induced hepatotoxicity. To test this hypothesis, the number of circulating blood platelets was decreased by the administration of an anti-rat platelet serum (APS) before LPS administration. The consequent thrombocytopenia by APS administration was associated with an attenuation of both LPS-induced liver injury and the activation of the coagulation system. However, the APS treatment did not prevent the hepatic neutrophil accumulation. These results suggest that platelets contribute to the pathogenesis of liver injury after LPS administration, perhaps through their integral role in coagulation and/or interaction with neutrophils, but they do not appear to contribute to hepatic neutrophil accumulation.
Pearson
J M
JM
Department of Pharmacology, Michigan State University East Lansing.
Schultze
A E
AE
Jean
P A
PA
Roth
R A
RA
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D004926:Escherichia coli; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000473:pathology*; D009336:Necrosis; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology*; D010976:Platelet Count; D051381:Rats; D017207:Rats, Sprague-Dawley; D013921:Thrombocytopenia / Q000097:blood / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen; D000410:Alanine Transaminase