The pathophisiologic role of hepatic lectin (asialoglycoprotein receptor) on immune mdiated liver cell injury in chronic liver diseases.

肝凝集素（脱唾液酸糖蛋白受体）对慢性肝病免疫介导的肝细胞损伤的病理生理学作用。

• 批准号: 04670445
• 负责人: ZENIYA Mikio
• 金额: $ 1.34万
• 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 General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670445/
• 关键词: Autoimmune hepatitis; Asialoglycoprotein receptor; T cell receptor; T cell receptor gene subfamily(Vbeta); annexin; 漫性肝炎; 免疫学的肝障害

Asialoglycoprotein receptor(ASGPR), hepatic lectin, is known as the liver specific glycoprotein. Previous reports suggested that this glycoprotein might be one of the candidate on immune-mediated liver cell injury especially in autoimmune hepatitis (AIH).Is this study, to clarify the immune-mechnism of liver cell damage, we tried to establish the assay system of antibody to ASGPR, and analyze the pathophisiology of this antibody in the course of chronic hepatitis. ASGPR was purified from human liver obtained from autopsied samples. A piece of liver was homogenated and separated by affinity Sepharose 4Bcolumn conjugated orthomucoid which has specific binding activity to ASGPR.The purified sample was tested by PAGE, and provided for the assay of anti-ASGPR antibody by western blotting. However immunoblotting analysis was not successful because of the existence of severe smear results. We made synthesized peptides of ASGPR and examined the proliferative activity of peripheral lymphocyte against them. These resulted poor responses, indicating the possibility that there was no ASGPR-specific T lymphocytes in peripheral lymphocytes. We studied TCR V beta repatore of peripheral and liver-infiltrated lymphocytes and it became clear that the TCR V beta repatore of liverinfiltrating lymphocytes was different from that of peripheral lymphocytes.

去唾液酸糖蛋白受体（ASGPR）是肝脏凝集素，是肝脏特异性糖蛋白.本研究试图建立抗ASGPR抗体的检测体系，并分析其在慢性肝炎发病过程中的病理机制，以阐明ASGPR在肝细胞损伤中的免疫机制。ASGPR从尸检样品获得的人肝脏中纯化。取肝组织匀浆，经Sepharose 4B亲和层析柱分离，纯化后的样品经聚丙烯酰胺凝胶电泳（PAGE）检测，并用于免疫印迹法检测抗ASGPR抗体。然而，免疫印迹分析是不成功的，因为存在严重的涂片结果。我们合成了ASGPR多肽，并检测了外周血淋巴细胞对它们的增殖活性。这些结果导致反应差，表明外周淋巴细胞中可能没有ASGPR特异性T淋巴细胞。我们研究了外周血和肝脏浸润淋巴细胞的TCR V β受体，发现肝脏浸润淋巴细胞的TCR V β受体不同于外周血淋巴细胞。

项目成果

Toda G, Zeniya: "Pathophisiology of autoimmune hepatitis." Jap J Med.82. 1403-1408 (1993)

Toda G，Zeniya：“自身免疫性肝炎的病理学。”

戸田剛太郎ほか: "自己免疫性肝疾患の病態" 日内誌. 82. 1403-1408 (1993)

Gotaro Toda 等：“自身免疫性肝病的病理学” Nichinai Shi. 82. 1403-1408 (1993)

唐沢 達信,銭谷 幹男他: "HBV Dre-Core領域の変異 Stop codonの形成とB型肝炎の病態との関連" 日本臨床. 51. 286-291 (1992)

Tatsunobu Karasawa、Mikio Zeniya 等人：“HBV Dre-Core 区域的突变：终止密码子形成与乙型肝炎病理学之间的关系”日本临床研究 51. 286-291 (1992)。

ZENIYA.M.et al.: "HCV-marker-positive autoimmune type chronic active hepatitis-possible relation between HCV ingection and liver autoreaction" Liver. (in press). (1994)

ZENIYA.M.等人：“HCV标记物阳性自身免疫型慢性活动性肝炎-HCV感染与肝脏自身反应之间的可能关系”肝脏。

ZENIYA,M.et al.: "Immunogenetic backgroaud of hepatitis Buirus iufection and autoimmuneepatitis in Japan" Gastroenterologia Jap.28(suppl). 70-75 (1993)

ZENIYA,M.等人：“日本布氏肝炎感染和自身免疫性肝炎的免疫遗传学背景”Gastroenterologia Jap.28（增刊）。