胆管消失症候群の免疫病理学的検討: 原発性胆汁性肝硬変を中心に

Material type: 文書・図像類

Author: 中沼, 安二ほか

Publisher: 金沢大学医学部

Publication date: 1995-03-01

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Note (General)：: 胆管系の代表的疾患群である胆管消失症候群の病態と病因を免疫病理学的に検討した。1.わが国での胆管消失症候群として、原発性胆汁性肝硬変が最も多く、次いで原発性硬化性胆管炎で、骨髄移植例に伴う移植片対宿主反応による胆管消失例や薬剤性胆管消失例もみられた。2.原発性胆汁性肝硬変の自己抗原はミトコンドリア内...

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Material Type: 文書・図像類
Title: 胆管消失症候群の免疫病理学的検討: 原発性胆汁性肝硬変を中心に
Author/Editor: 中沼, 安二
Nakanuma, Yasuni
Author Heading: 中沼, 安二
Nakanuma, Yasuni
Publication, Distribution, etc.: 金沢大学医学部
Publication Date: 1995-03-01
Publication Date (W3CDTF): 1995-03-01
Alternative Title: Immunopathological study of vanishing bile duct syndrome with emphasis on primary biliary cirrhosis
Periodical title: 平成6(1994)年度科学研究費補助金一般研究(B) 研究成果報告書 = 1994 Fiscal Year Final Research Report
No. or year of volume/issue: 1993-1994
Volume: 1993-1994
Pages: 8p.-
Text Language Code: jpn
Subject Heading: 胆管消失症候群
原発生胆汁性肝硬変
原発性硬化性胆管炎
胆管上皮
細胞接着分子
サイトカイン
細胞培養
免疫病理
vanishing bile duct syndrome
primary biliary cirrhosis
primary sclerosing cholangitis
biliary epithelium
cellular adhesion molecules
cytokines
cell culture
immunopathology
Target Audience: 一般
Note (General): 胆管系の代表的疾患群である胆管消失症候群の病態と病因を免疫病理学的に検討した。1.わが国での胆管消失症候群として、原発性胆汁性肝硬変が最も多く、次いで原発性硬化性胆管炎で、骨髄移植例に伴う移植片対宿主反応による胆管消失例や薬剤性胆管消失例もみられた。2.原発性胆汁性肝硬変の自己抗原はミトコンドリア内膜上のピルビン酸脱水素酵素のE2成分である。この酵素に対するモノクローナル抗体で原発性胆汁性肝硬変患者の肝臓を免疫染色した結果、障害胆管ではミトコンドリア以外の細胞質が陽性となり、molecular mimicryが病因として示唆された。3.肝内胆管に分布する胆管周囲脈管叢の病理像を検討した。原発性胆汁性肝硬変では、免疫反応に伴った内皮細胞の変化がみられた。原発性硬化性胆管炎では、血管叢に明かな消失があり、循環障害が成因の一部と考えられた。4.原発性胆汁性肝硬変の障害胆管とその周囲の微小環境を検討した結果、ICAM-1やVCAM-1等の細胞接着因子の異常発現が胆管周囲の小血管や胆管上皮にみられ、CD4、CD8陽性のeffector lymphocytesの高度浸潤がみられた。胆管上皮の障害とその微小環境の異常が胆管障害に重要と考えられた。5.マウスの肝内胆管上皮の区分別培養に成功した。胆管樹を作成し、胆管区分を実体顕微鏡下で細切し、コラーゲンゲル内および上で培養し、胆管上皮細胞の純化に成功した。次に、培地中にIFN-γ、TNF-α等のサイトカインを添加し、胆管上皮にHLA-DRやHLA-A,B,C等の抗原が発現されることを示した。6.ANIT等の胆管障害剤と免疫操作の組み合わせで実験的胆管炎を作成し、胆管上皮の壊死とアポトーシスが種々の割合でみられた。ヒトの胆管消失症候群でも壊死+アポトーシスの所見がみられ、この動物のモデルがヒトの胆管消失症候群の病態解明に応用出来ると期待された。
Vanishing bile duct syndrome was examined immunopathologically with emphasis on etiology and pathogenesis. 1. Among this syndrome in Japan, primary biliary cirrhosis was most frequent, and the next was primary sclerosing cholangitis. Graft-versus-host disease related to bone marrow transplantation and drug-induced bile duct loss were also occasionally encoutered. 2. In primary biliary cirrhosis, pyruvate dehydrogenase complex E2 on mitochondrial inner membrane was regarded as an autoantigen. Immunohistochemical study using monoclonal antibody disclosed that this complex was aberrantly expressed outside mitochondria, suggesting molecular mimicry pathogenesis of this disease. 3. Peribiliary vascular plexus, a system of blood supply to the bile ducts, was involved immunologically in primary biliary cirrhosis and makedly diminished in primary sclerosing cholangitis. These changes may be related to their pathogenesis. 4. Around the damaged bile ducts of primary biliary cirrhosis, abnormal e xpression of abhesion molecules such as ICAM-1 and VCAM-1 on the endothelial cells and adso bile duct epithelium, were found. Marked infiltration of CD4 and CD8 positive lymphoid cells were also found around these ducts. These abnomal microenviroments may be involved in the pathogenesis of primary biliary cirrhosis. 5. Selective culture of biliary tree was methodologically established, using collagen gel. By this method, it was found that addition of cytokines such as INF-gamma induced abnormal expression of HLA-DR or HLA-A,B,C on cultured bile duct epithelium. Further analysis of biological phenomenon of ductal epitelium of vanishing bile duct syndrome will be expected. 6. Combination of hepatotoxic drugs and immunomodulation created pecular bile duct damages in experimental models, presenting biliary cell necrosis and apoptosis. The latter finding were also found in damaged bile ducts in vanishing bile duct syndrome, suggesting that our animal models could be applied to the evaluation of human vanishing bile duct syndrome.
研究課題/領域番号:05454175, 研究期間(年度):1993–1994
出典：「胆管消失症候群の免疫病理学的検討: 原発性胆汁性肝硬変を中心に」研究成果報告書　課題番号05454175(KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作成
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/search/?qm=10115256
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05454175/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-05454175/054541751994kenkyu_seika_hokoku_gaiyo/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA