Essential roles of the Fas ligand in the development of hepatitis
Essential roles of the Fas ligand in the development of hepatitis
复制标题
DOI：
10.1038/nm0497-409
复制
发表时间：
1997-04-01
期刊：
影响因子：
82.9
通讯作者：
Nagata, S
中科院分区：
文献类型：
--
作者：
Kondo, T;Suda, T;Nagata, S
Fas配体(FasL)在活化的T细胞中表达，并诱导Fas阳性细胞的凋亡。针对乙肝表面抗原(HBs)的细胞毒性T淋巴细胞(CTL)克隆可引起HBs Ag转基因小鼠的急性肝病。在这里，我们观察到CTL克隆以Fas依赖的方式杀死了表达乙肝表面抗原的肝细胞。将可溶性Fas导入HBs Ag转基因小鼠，可预防CTL诱导的肝病。在第二种模型中，给小鼠注射痤疮丙酸杆菌。随后用脂多糖(LPS)攻击小鼠，造成肝脏损伤，导致小鼠死亡。FasL的中和使小鼠免于脂多糖诱导的死亡，Fas缺失的小鼠对脂多糖诱导的死亡具有抵抗力。这些结果提示FasL在肝炎的发生发展中起着重要作用。
The Fas ligand (FasL) is expressed in activated T cells and induces apoptosis in Fas-bearing cells. A cytotoxic T lymphocyte (CTL) clone specific for hepatitis B surface antigen (HBsAg) causes an acute liver disease in HBsAg transgenic mice. Here we observed that the CTL clone killed hepatocytes expressing HBsAg in a Fas-dependent manner. Administration of the soluble form of Fas into HBsAg transgenic mice prevented the CTL-induced liver disease. In the second model, mice were primed with Propionibacterium acnes. A subsequent challenge with lipopolysaccharide (LPS) killed the mice by inducing liver injury. Neutralization of FasL rescued the mice from LPS-induced mortality, and Fas-null mice were resistant to LPS-induced mortality. These results suggest that FasL has an essential role in the development of hepatitis.