Importance of Kupffer cells for T-cell-dependent liver injury in mice
Importance of Kupffer cells for T-cell-dependent liver injury in mice
复制标题
DOI：
10.1016/s0002-9440(10)64804-3
复制
发表时间：
2000-11-01
影响因子：
6
通讯作者：
Tiegs, G
中科院分区：
文献类型：
--
作者：
Schümann, J;Wolf, D;Tiegs, G
在任何类型的急性肝炎中，T细胞似乎都是造成肝损伤的原因。然而，枯否细胞（KCs）对T细胞依赖性肝功能衰竭的重要性尚不清楚。本文着重研究了小鼠T细胞刺激后KCs和肿瘤坏死因子（TNF）的作用。假单胞菌外毒素A（PEA）、伴刀豆球蛋白A（ConA）或亚毒性剂量的PEA和超抗原葡萄球菌肠毒素B（SE B）的组合均可诱导T细胞和TNF依赖性肝损伤。氯膦酸盐脂质体可耗竭KC。在ConA处理的小鼠的肝脏中几乎没有观察到任何凋亡细胞。相反，可见大的桥接坏死。KCs的消除可保护小鼠免受PEA、Con A或PEA/SEB诱导的肝损伤。在没有KC的情况下，肝损伤仅限于少数小的坏死区域。KC是TNF的主要来源。肝TNF mRNA和蛋白质的产生强烈衰减，因为KC消耗，而血浆TNF水平不变。我们的结果表明，KCs在T细胞活化诱导的肝损伤中发挥重要作用，通过贡献TNF。血浆TNF水平是TNF依赖性肝脏炎症严重程度的不良诊断标志物。
T cells seem to be responsible for liver damage in any type of acute hepatitis. Nevertheless, the importance of Kupffer cells (KCs) for T-cell-dependent liver failure is unclear. sere we focus on the role of KCs and tumor necrosis factor (TNF) production after T cell stimulation in mice. T-cell- and TNF-dependent liver injury were induced either by Pseudomonas exotoxin A (PEA), by concanavalin A (Con A), or by the combination of subtoxic doses of PEA and the superantigen Staphylococcus enterotoxin B (SEB), KCs were depleted by clodronate liposomes, Although livers of PEA-treated mice contained foci of confluent necrosis and numerous apoptotic cells, hardly any apoptotic cells were observed in the livers of Con A-treated mice. Instead, large bridging necroses were visible. Elimination of KCs protected mice from PEA-, Con A-, or PEA/SEB-induced liver injury. In the absence of KCs, liver damage was restricted to a few small necrotic areas. KCs were the main source of TNF. Hepatic TNF mRNA and protein production were strongly attenuated because of KC-depletion whereas plasma TNF levels were unaltered. Our results suggest that KCs play an Important role in T cell activation-induced liver injury by contributing TNF. Plasma TNF levels are poor diagnostic markers for the severity of TNF-dependent liver inflammation.