Regulatory mechanisms of apoptosis via AIM in fulminant hepatitis model.

炎症性疾病的一个特征是渗入的淋巴细胞、中性粒细胞和巨噬细胞对组织细胞的破坏。靶组织和浸润性细胞的细胞凋亡调控是决定炎症发生和发展的关键事件之一。我们最近分离到一种新的凋亡抑制因子，称为AIM，它是由组织巨噬细胞分泌的。在这份报告中，我们提出了与肝脏炎症(肝炎)相关的AIM的独特特征，通过在体内过度表达AIM的AIM转基因小鼠和正常小鼠中引入一种实验性暴发性肝炎来鉴定。从转基因小鼠肝脏中观察到的巨噬细胞数量的显著增加来看，AIM似乎抑制了炎症区域的巨噬细胞的死亡。此外，AIM还能增强巨噬细胞的吞噬功能。此外，还发现了AIM的其他新功能。这些是，AIM通过抑制T细胞和自然杀伤(NK)T细胞的凋亡来抑制肉芽肿的进展，以及AIM诱导B淋巴细胞的生长抑制。在此基础上，我们提出AIM可能也参与了自身免疫性疾病--原发性胆汁性肝硬变(PBC)的疾病进展，并导致肝炎。通过原位检测，AIM mRNA在胆管炎症部位表达上调。AIM可能影响多种炎症反应。研究AIM的作用可能会引起极大的兴趣。

A hallmark of inflammatory disease is the destruction of tissue cells by infiltrating lymphocytes, neutrophils and macrophages. The regulation of apoptosis of both target tissues and the infiltrating cells is one of the key events that defines the initiation and the progression of inflammation. We recently isolated a novel apoptosis inhibitory factor, termed AIM, which is secreted by tissue macrophages. In this report, we present unique characteristics of AIM associated with liver inflammation (hepatitis), identified by introducing an experimental fulminant hepatitis in both AIM-transgenic mice, which overexpressAIM in the body, and normal mice. AIM appears to inhibit the death of macrophages in the inflammatory regions, judging by the remarkably increased number of macrophages observed in the liver from transgenic mice. In addition, AIM also enhances the phagocytosis by macrophages. Moreover, other new functions of AIM are found. These are, AIM tempers granuloma progression by inhibiting apoptosis of T and natural killer (NK) T cells, and AIM induces growth inhibition of B lymphocytes. Based on these, we make hypothesis that AIM may also contribute to the disease progression of primary biliary cirrhosis (PBC), which is a kind of autoimmune diseases, and causes hepatitis. By in situ assay, AIM mRNA expression is upregulated at the site of inflammations in bile ducts. AIM might affect many kinds of inflammation. To study the role of AIM might be of great interest.