Tsutsui H, Mizoguchi Y, Morisawa S
First Department of Biochemistry, Osaka City University Medical School, Japan.
Hepatogastroenterology. 1992 Dec;39(6):553-9.
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.
当将脂多糖给予已注射热灭活痤疮丙酸杆菌的小鼠时，它们中的大多数死于大规模肝坏死。此前，我们证明，由痤疮丙酸杆菌和脂多糖共同充分激活的肝黏附细胞释放的一种可溶性肝细胞毒性因子可归因于这种严重肝损伤的晚期。在本报告中，我们聚焦于这些肝黏附细胞以细胞间相互作用的方式导致的肝细胞溶解。在用脂多糖刺激后不久，痤疮丙酸杆菌诱导的肝黏附细胞几乎完全杀死了从正常同基因小鼠和经痤疮丙酸杆菌处理的小鼠制备的肝细胞。由于痤疮丙酸杆菌诱导的肝黏附细胞也被证明能在短时间内产生多种细胞因子，因此分析了细胞因子在这种肝损伤中的作用。只有肿瘤坏死因子-α能使痤疮丙酸杆菌诱导的肝黏附细胞杀死从相同小鼠而非正常小鼠制备的肝细胞。这些结果表明，经痤疮丙酸杆菌处理而积累并部分被激活的肝黏附细胞一旦被脂多糖触发，可能会迅速裂解自体肝细胞，并且这些肝黏附细胞产生的肿瘤坏死因子-α可能会上调它们自身的肝细胞毒性能力。
