Potential role of hepatic macrophages in neutrophil-mediated liver injury in rats with sepsis.
We investigated the pathogenesis of septic liver injury in rats caused by cecal ligation and puncture. In this model, numerous neutrophils accumulated in the liver in parallel with the development of liver dysfunction. The supernatants of hepatic macrophages isolated from these septic rats 24 hr after cecal ligation and puncture had enhanced chemotactic activities for human neutrophils. These results suggest that in sepsis, hepatic macrophages attract neutrophils to the liver. Human neutrophils preincubated in this macrophage supernatant had the following biological activities not seen in the sham-operated controls. (a) They became more adherent to cultured endothelial cells through up-regulation of adhesion molecules such as CD11b/CD18, (b) their chemiluminescence was markedly elevated. These functional changes of cecal ligation and puncture hepatic macrophages were the same as those in endotoxin-pretreated hepatic macrophages after isolation from normal rats. Therefore we suspect that hepatic macrophages are activated by portal vein endotoxin in sepsis. These activated hepatic macrophages secreted chemical mediators of inflammation, including leukotriene B4 and tumor necrosis factor. In conclusion, hepatic macrophages seem to interact closely with neutrophils and play an important role in the pathogenesis of septic liver injury.
Doi
F
F
First Department of Surgery, Kyushu University School of Medicine, Fukuoka, Japan.
Goya
T
T
Torisu
M
M
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001158:Arteries; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000502:physiology; D004731:Endotoxins / Q000097:blood; D007975:Leukotriene B4 / Q000378:metabolism; D008099:Liver / Q000473:pathology* / Q000503:physiopathology; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4