Importance of direct hepatocytolysis by liver macrophages in experimental fulminant hepatitis.
When lipopolysaccharide was administered to mice that had been injected with heat-killed Propionibacterium acnes, most of them died of massive liver necrosis. Previously, we demonstrated that a soluble hepatocytotoxic factor released by liver adherent cells fully activated by both P. acnes and lipopolysaccharide was attributable to the late stage of this severe liver injury. In this report, we focused on the hepatocytolysis by these liver adherent cells in a cell-cell interaction manner. Shortly after stimulation with lipopolysaccharide, the P. acnes-elicited liver adherent cells almost completely killed the hepatocytes prepared from both normal syngeneic mice and P. acnes-treated ones. Since P. acnes-elicited liver adherent cells also proved to produce various kinds of cytokines in a short time, the role of cytokines in this liver injury was analyzed. Only TNF-alpha enabled the P. acnes-elicited liver adherent cells to kill hepatocytes prepared from the same mice, but none from the normal ones. These results suggest that the liver adherent cells accumulated and partly stimulated by P. acnes-treatment might rapidly lyse the autologous hepatocytes once triggered by lipopolysaccharide and that the TNF-alpha these liver adherent cells produced might upregulate their own hepatocytotoxic ability.
Tsutsui
H
H
First Department of Biochemistry, Osaka City University Medical School, Japan.
Mizoguchi
Y
Y
Morisawa
S
S
D000208:Acute Disease; D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D016207:Cytokines / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D006501:Hepatic Encephalopathy / Q000276:immunology / Q000473:pathology*; D006524:Hepatitis, Viral, Animal / Q000276:immunology / Q000473:pathology*; D007375:Interleukin-1 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver / Q000473:pathology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011425:Propionibacterium acnes; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha