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Mechanism of hepatocyte injury in autoimmune hepatitis : involvement of hepatic sinusoidal endothelial cell injury.

自身免疫性肝炎肝细胞损伤的机制：肝窦内皮细胞损伤。

基本信息

批准号：
07457142
负责人：
TODA Gotaro
金额：
$ 4.86万
依托单位：
The Jikei University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

There have been several lines of evidence indicating that antibody-dependent cell-mediated cytotoxicity (ADCC) is involved in the development and perpetuation of hepatocyte injury in autoimmune hepatitis (AIH). Using rat hepatic sinusoidal endothelial cells as the substrate, we looked for the antibody to these cells in the sera of patients with chronic liver diseases. The antibody was detected in 97.1% of AIH patients examined. In the patients with chronic hepatitis (CH) B,CH-C and primary biliary cirrhosis, the positivity rates were 7.9,5.9 and 13.0%, respectively. Thus the occurrence of the antibody charactrized AIH.We also found that the antibody was cytotoxic to hepatic sinusoidal endothelial cells, suggesting that the endothelial cell injury by this antibody induced micro-circulatory disturbance, leading to hepatocyte injury. Incubation of F(ab')_2 from sera of patients with bovine carotid artery endothelial cell, not with rat hepatocyte and dRLh84 cell, diminished the reactivity with hepatic sinusoidal endothelial cell, suggesting that the antibody recognized the endothelial cell-specific antigen. The antibody was also detected when human umblical vascular endothelial cell and human hepatic sinusoidal endothelial cell was used as the substrate. We reported the occurrence of antisulfatide antibody in sera of patients with autoimmune hepatitis. The antisulfatide antibody was cross-reactive with heparin, suggesting that this antibody was reactive with the endothelial cell and the same as the antibody to endothelial cell.

已有多项证据表明，抗体依赖性细胞介导的细胞毒性（ADCC）参与了自身免疫性肝炎（AIH）肝细胞损伤的发生和持续。以大鼠肝窦内皮细胞为底物，在慢性肝病患者血清中寻找抗肝窦内皮细胞的抗体。AIH患者血清中抗体阳性率为97.1%。慢性B型肝炎、慢性丙型肝炎和原发性胆汁性肝硬化患者的阳性率分别为7.9%、5.9%和13.0%。本研究还发现该抗体对肝窦内皮细胞具有细胞毒性，提示该抗体损伤内皮细胞引起微循环障碍，导致肝细胞损伤。病人血清F（ab '）_2与牛颈动脉内皮细胞孵育后，与肝窦内皮细胞的反应性减弱，提示该抗体识别内皮细胞特异性抗原。以人脐静脉内皮细胞和人肝窦内皮细胞为底物，也可检测到抗体。本文报告了自身免疫性肝炎患者血清中抗硫脂抗体的发生。抗硫脂抗体与肝素有交叉反应，提示该抗体与内皮细胞抗体反应一致，与内皮细胞抗体反应一致。