Toshima K, Mochida S, Ishikawa K, Matsui A, Arai M, Ogata I, Fujiwara K
Third Department of Internal Medicine, Saitama Medical School, Japan.
Biochem Biophys Res Commun. 1998 May 29;246(3):731-5. doi: 10.1006/bbrc.1998.8692.
Activated Kupffer cells and hepatic macrophages can produce massive liver necrosis through microcirculatory disturbance due to sinusoidal fibrin deposition. This mechanism is involved in the development of liver injury after endotoxin administration in rats pretreated with heat-killed Propionibacterium acnes (P.acnes) or undergoing 70% liver resection. The significance of CD14, a receptor for lipopolysaccharide and its binding protein, was evaluated in both models in relation to the activation mechanisms of Kupffer cells and hepatic macrophages. Northern blot analysis revealed that CD14 mRNA expression was increased in the liver of rats following P.acnes administration. In these rats, hepatic macrophages immediately after isolation showed marked increased of CD14 mRNA expression compared to Kupffer cells from normal rats. In contrast, CD14 mRNA expression was minimal in partially resected liver. Interleukin (IL)-18 and IL-2 mRNA expression in the liver and interferon (IFN)-gamma mRNA expression in the spleen were significantly increased in P.acnes-treated rats compared to normal rats, while these increases were absent in partially hepatectomized rats. Thus, CD14 expressed on hepatic macrophages after activation through a cytokine network of IL-18, IFN-gamma, and IL-2 may contribute to endotoxin-induced liver injury in P.acnes-treated rats. In contrast, in partially hepatectomized rats, this network may not operate during Kupffer cell activation, and the liver injury might develop through endotoxin receptors other than CD14 on the cells.
活化的库普弗细胞和肝巨噬细胞可通过肝血窦纤维蛋白沉积导致的微循环障碍引发大规模肝坏死。在用热灭活痤疮丙酸杆菌（P.acnes）预处理或接受70%肝切除的大鼠中，该机制参与了内毒素给药后肝损伤的发展。在这两种模型中，针对脂多糖受体CD14及其结合蛋白，就库普弗细胞和肝巨噬细胞的激活机制进行了评估。Northern印迹分析显示，给予P.acnes后大鼠肝脏中CD14 mRNA表达增加。在这些大鼠中，分离后的肝巨噬细胞与正常大鼠的库普弗细胞相比，CD14 mRNA表达显著增加。相反，在部分切除的肝脏中，CD14 mRNA表达极少。与正常大鼠相比，P.acnes处理的大鼠肝脏中白细胞介素（IL）-18和IL-2 mRNA表达以及脾脏中干扰素（IFN）-γ mRNA表达显著增加，而在部分肝切除的大鼠中则无这些增加。因此，通过IL-18、IFN-γ和IL-2的细胞因子网络激活后，肝巨噬细胞上表达的CD14可能导致P.acnes处理的大鼠发生内毒素诱导的肝损伤。相反，在部分肝切除的大鼠中，该网络在库普弗细胞激活过程中可能不起作用，肝损伤可能通过细胞上除CD14以外的内毒素受体发展。
