Hayashi N, Mita E
First Department of Medicine, Osaka University School of Medicine, Japan.
J Gastroenterol Hepatol. 1997 Oct;12(9-10):S223-6. doi: 10.1111/j.1440-1746.1997.tb00504.x.
Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the major causative agents of chronic liver disease. However, the mechanisms responsible for liver cell injury remain to be clarified. Playing crucial roles in the clearance of viral infection are cytotoxic T lymphocytes. Recently, it has been demonstrated that perforin- and Fas-based mechanisms account for all T cell-mediated cytotoxicity. Therefore, we examined the correlation between liver cell damage and the Fas system in the liver of patients with chronic hepatitis C. Fas is a cell surface protein that mediates apoptosis with treatment of the Fas ligand or the anti-Fas antibody. To investigate the role of Fas in type C hepatitis, we examined the correlation between liver cell damage and Fas expression. Fas expression was found mainly in the cytoplasm of hepatocytes and these positive cells were found particularly among infiltrating lymphocytes. A high prevalence of Fas expression was shown in liver tissue with more severe inflammation. The Fas system-mediated death signal requires the interaction of Fas ligand with Fas on target cells. We isolated a 1.9 kb cDNA clone for the human Fas ligand and examined the expression of the Fas ligand in liver-infiltrating mononuclear cells obtained from patients with chronic hepatitis C. The open reading frame encodes 281 amino acids. Next, we examined the expression of the Fas ligand in liver-infiltrating mononuclear cells obtained from patients with chronic hepatitis C. The amplified products (231 bp) derived from Fas ligand transcripts were detected in liver-infiltrating mononuclear cells, whereas no signal was observed in liver tissues. In HCV infection, Fas expression in hepatocytes is up-regulated in accordance with the severity of liver inflammation. When HCV-specific T cells migrate into hepatocytes and recognize the viral antigen via the T cell receptor, they become activated and express Fas ligand that can transduce the apoptotic death signal to Fas-bearing hepatocytes. Thus, the Fas system plays an important role in liver cell injury by HCV infection.
丙型肝炎病毒（HCV）和乙型肝炎病毒（HBV）是慢性肝病的主要致病因素。然而，导致肝细胞损伤的机制仍有待阐明。细胞毒性T淋巴细胞在清除病毒感染中起关键作用。最近，已证明基于穿孔素和Fas的机制是所有T细胞介导的细胞毒性的原因。因此，我们研究了慢性丙型肝炎患者肝脏中肝细胞损伤与Fas系统之间的相关性。Fas是一种细胞表面蛋白，在受到Fas配体或抗Fas抗体作用时介导细胞凋亡。为了研究Fas在丙型肝炎中的作用，我们研究了肝细胞损伤与Fas表达之间的相关性。发现Fas表达主要存在于肝细胞的细胞质中，并且这些阳性细胞尤其在浸润淋巴细胞中发现。在炎症更严重的肝组织中显示出Fas表达的高发生率。Fas系统介导的死亡信号需要Fas配体与靶细胞上的Fas相互作用。我们分离出了人Fas配体的1.9 kb cDNA克隆，并检测了从慢性丙型肝炎患者获得的肝浸润单核细胞中Fas配体的表达。开放阅读框编码281个氨基酸。接下来，我们检测了从慢性丙型肝炎患者获得的肝浸润单核细胞中Fas配体的表达。在肝浸润单核细胞中检测到源自Fas配体转录本的扩增产物（231 bp），而在肝组织中未观察到信号。在HCV感染中，肝细胞中的Fas表达根据肝脏炎症的严重程度而上调。当HCV特异性T细胞迁移到肝细胞中并通过T细胞受体识别病毒抗原时，它们被激活并表达Fas配体，该配体可以将凋亡死亡信号传递给带有Fas的肝细胞。因此，Fas系统在HCV感染引起的肝细胞损伤中起重要作用。
