Interferon-gamma-mediated tissue factor expression contributes to T-cell-mediated fulminant hepatitis through induction of hyper coagulation in mice

伴刀豆球蛋白A（Con A）治疗以依赖于干扰素（IFN）-γ的方式诱导小鼠暴发性肝炎。如前所述，尽管IFN-γ的产生是健康的，但用抗凝肝素治疗可以预防Con A肝炎。在这里，我们调查了高凝介导的肝炎的机制。IFN-γ缺乏的小鼠对Con A肝炎具有抗性，而不会诱导全身和肝脏高凝状态。这表明IFN-γ是血栓相关变化所必需的。中和组织因子，这是必要的激活凝血级联反应，导致这种肝炎的保护，尽管正常诱导IFN-γ。肝巨噬细胞和内皮细胞对IFN-γ的反应性是必需的，它们在Con A激发后表达组织因子。因此，IFN-γ在各种肝细胞中引起的促炎信号对于Con A肝炎的发展是必要的。

Concanavalin A (Con A) treatment induces fulminant hepatitis in mice in a manner dependent on interferon (IFN)-gamma. As previously reported, treatment with the anticoagulant heparin protects against Con A hepatitis, despite healthy production of IFN-gamma. Here, we investigated the mechanisms for hypercoagulation-mediated hepatitis. Mice deficient in IFN-gamma were resistant to Con A hepatitis without induction of systemic and hepatic hypercoagulation. This suggests that IFN-gamma is necessary for the thrombus-associated changes. Neutralization of tissue factor, that is essential for the activation of coagulation cascade, resulted in the protection of this hepatitis despited normal induction of IFN-gamma. Responsiveness to IFN-gamma was required for both hepatic macrophages and endothelial cells, which expressed tissue factor after Con A challenge. Thus, proinflammatory signal elicited by IFN-gamma in various liver cells is necessary for the development of Con A hepatitis.