Mochida S, Ohno A, Arai M, Fujiwara K
Third Department of Internal Medicine, Saitama Medical School, Japan.
J Gastroenterol Hepatol. 1995;10 Suppl 1:S38-42. doi: 10.1111/j.1440-1746.1995.tb01795.x.
Sinusoidal endothelial cell damage is produced by activation of hepatic macrophages after endotoxin administration in rats pretreated with Cornyebacterium parvum or undergoing 70% hepatectomy. Such damage causes fibrin deposition in the hepatic sinusoids leading to massive hepatic necrosis. In the C. parvum model, cytotoxic mediators, such as tumour necrosis factor (TNF)alpha and superoxide anions released from activated hepatic macrophages directly destroy sinusoidal endothelial cells. In contrast, in the partial hepatectomy model, endothelial cell damage occurs as a result of fibrin deposition due to derangement of the coagulation equilibrium regulated by tissue factor and thrombomodulin expressed on hepatic macrophages and sinusoidal endothelial cells, respectively. Immunohistological examination revealed that the expression of ICAM-1 in sinusoidal endothelial cells and LFA-1 in hepatic macrophages was greater in both models than in normal rats preceding the development of hepatic necrosis. The extent of liver injury was significantly attenuated by treatment with monoclonal antibodies against both adhesion molecules in the C. parvum model, but aggravated in the partial hepatectomy model, compared to control rats. We conclude that adhesion of activated macrophages to endothelial cells via LFA-1 and ICAM-1 in the hepatic sinusoids is essential for endothelial cell destruction in the C. parvum model, but can act protectively against provocation of fibrin deposition in the hepatectomy model.
在用短小棒状杆菌预处理或接受70%肝切除的大鼠中，内毒素给药后肝巨噬细胞激活可导致肝血窦内皮细胞损伤。这种损伤会导致肝血窦内纤维蛋白沉积，进而引发大规模肝坏死。在短小棒状杆菌模型中，细胞毒性介质，如肿瘤坏死因子（TNF）α和活化肝巨噬细胞释放的超氧阴离子，直接破坏血窦内皮细胞。相比之下，在部分肝切除模型中，内皮细胞损伤是由于分别由肝巨噬细胞和血窦内皮细胞表达的组织因子和血栓调节蛋白调节的凝血平衡紊乱导致纤维蛋白沉积所致。免疫组织学检查显示，在肝坏死发生之前，两种模型中血窦内皮细胞中ICAM - 1的表达和肝巨噬细胞中LFA - 1的表达均高于正常大鼠。在短小棒状杆菌模型中，用针对两种黏附分子的单克隆抗体治疗可显著减轻肝损伤程度，但与对照大鼠相比，在部分肝切除模型中则会加重肝损伤。我们得出结论，在短小棒状杆菌模型中，活化巨噬细胞通过LFA - 1和ICAM - 1与肝血窦内皮细胞的黏附对于内皮细胞破坏至关重要，但在肝切除模型中可对纤维蛋白沉积的激发起到保护作用。
