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 antagonist) 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 GalN-LPS administration was not reduced by WEB 2086, hepatic injury and hepatic neutrophil accumulation in the liver after GalN-LPS administration were attenuated by WEB 2086. An in vitro study revealed that an enhanced neutrophil adhesion to hepatic endothelial cells by stimulation with the sera that were collected from the GalN-LPS-treated rats, was 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 presence of WEB 2086. These results suggest that PAF play an important role in the GalN-LPS induced hepatic injury and that PAF receptor antagonist reduces the neutrophil adherence to hepatic endothelial cells in the liver.
Komatsu
Y
Y
Department of Internal Medicine II and I, Faculty of Medicine, University of Tokyo, Japan.
Shiratori
Y
Y
Hikiba
Y
Y
Hashimoto
N
N
Han
K
K
Kawase
T
T
Yoshida
H
H
Okano
K
K
Omata
M
M
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D004727:Endothelium / Q000166:cytology / Q000187:drug effects; D004926:Escherichia coli; D005688:Galactosamine; D008070:Lipopolysaccharides; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D010972:Platelet Activating Factor / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects
D001381:Azepines; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C052518:WEB 2086; D005688:Galactosamine