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

Research Project

Project/Area Number 07457142
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionThe Jikei University School of Medicine

Principal Investigator

TODA Gotaro  The Jikei University School of Medicine, First Department of Internal Medicine, Professor, 医学部, 教授 (40090500)

Co-Investigator(Kenkyū-buntansha) ISHIKAWA Tomohisa  The Jikei University School of Medicine, First Department of Internal Medicine,, 医学部, 助手 (10260944)
TAKAHASHI Hiroki  The Jikei University School of Medicine, First Department of Internal Medicine,, 医学部, 助手 (80256403)
AIZAWA Yoshio  The Jikei University School of Medicine, First Department of Internal Medicine,, 医学部, 講師 (90147273)
ZENIYA Mikio  The Jikei University School of Medicine, First Department of Internal Medicine,, 医学部, 助教授 (70138767)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥5,500,000 (Direct Cost: ¥5,500,000)
Keywordsautoimmune hepatitis / hepatic sinusoidal endothelial cell / endothelial cell antibody / antisulfatide antibody / heparin / 類洞壁内皮細胞 / 類洞内皮細胞 / 内皮細胞 / 自己抗体 / 肝類洞内皮細胞
Research Abstract

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.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Kotsuken Han: "Occurrence of antibody against rat lepatic endo thelial cells in seia of patients with autoimmune lepatitis" Digestive Diseases and Science. 40. 1213-1220 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mikio Zeniya: "The ambomobulin expression of einusoidal endo thelial cells in chrovic viral hepatitis" J Gastroenterology and Hepatology. 10. S70-S80 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yusei Ikeda: "Crops-reactivity of antisulfatide antibody with sulfated glyconamiroglycaus in sera of patieuts with AIH" International Hepatology Communications. 4. 245-254 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Gotaro Toda: "Interferon or corticonteroid : treatment of patients with chionic hepatitis C positive for serum markeis of autoimmune disease" Internal Hedicine. 36. 233-235 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Gotaro Toda: "Present status of autoimmune hepatitis in Japan-corelatiny the characteristico with international criteria" J Hepatology. 26. 1207-1212 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Akihiro Hayashi: "Induction of autoimmune-like hepatic and ductal lesions by administiation of Les mice undergoing C-VH reaction acrous MH C class difference" Immunology Letters. 59. 646-653 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Gotaro Toda: "Molecular basis of autoimmune hepatitis. Immunogenetics of AIH in Japan(分理)" Springes Verlog,McfailaneIG,Wiuiams R 編, 05-128 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroki Takahashi: "Molecular basis of antoimmune hapatitis. The Japanese models of AIH (分理)" Springer Verag, Mcfarlane IG,Wiuiams R 編, 165-176 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Katsuken Han: "Occurrence of antibody against rat hepatic endothelial cells in sera of patients with autoimmune hepatitis." Digestive Diseases and Science. 40. 1213-1220 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mikio Zeniya: "Thrombomodulin expression of sinusoidal endothelial cells in chronic viral hepatitis." J.Gastroenterology and Hepatology. 10. S70-80 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yusei Ikeda: "Cross-reactivity of antisulfatide antibody with sulfated glycoaminoglycans in sera of patients with autoimmune hepatitis." International Hepatology Communications. 4. 245-254 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Gotaro Toda: "Interferon or corticosteroid : treatment of patients with chronic hepatitis C positive for serum markers of autoimmune disease" Internal Medicine. 36. 233-235 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Gotaro Toda: "Present status of autoimmune hepatitis in Japan-correlating the characteristics with international criteria in an area with a high rate of HCV infection." J.Hepatology. 26. 1207-1212 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Akihiro Hayashi: "Induction of autoiuume-like hepatic and ductal lesions by administration of LPS in mice undergoing graft-versus-host reaction across MHC class 1 difference" Immunology Letters. 59. 646-653 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Gotaro Toda: "Immunogenetics of autoimmune hepatitis in Japan" Molecular basis of autoimmune hepatitis. Springer Verlag, McFarlane IG and Williams R,eds.105-128 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroki Takahashi: "The Japanese models of Autoimmune hepatitis." Molecular basis of autoimmune hepatitis Springer Verlag, McFarlane IG and William R,eds.165-176 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Gotaro Toda: "Interferon or corticosteroid:Treatment of patients with chronic hepatitis C positive for serum markers of autoimmune disease" Internal M edicine. 36. 233-235 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Gotaro Toda: "Present status of autoimmune hepatitis in Japan-courelating the characteristics with international criteria・・・・・." J Hepatology. 26. 1207-1212 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Akihiro Hayashi: "Induction of autoimmune-like hepatic and ductal lecions by administration of LPS in mice undergoing GVH reaction across MHC class II difference" Immunology Letters. 59. 159-170 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 渡辺文時: "自己免疫性肝炎に対する活原とAIHスコアーの検討" 肝臓. 38. 646-653 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Katsuken Han: "Occurrence of antibody against rat hepatic endo thelial cells in sera of patients with autoimmune hepatitis" Digestive Diseases and Sciences. 40,6. 1213-1220 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mikio Zeniya: "Thrombomodulin expression of sinusordal endo thelial cells in chronic irral hepatitis" Journal of Gastioenteorogy and Hepatology. 10. S70-S80 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yusei Ikeda: "Croos-reactivity of anti-sulfatide antibody with eulfated glycoo aminoglycaus and DNA in seatron patients with AIH" International Hepatology Communications. 4. 245-254 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Gotaro Toda: "Immunogenetics of antoimmune hepatitis in Japan" Molecular Basis of Autoimmune Hepatitis (McEalane IG,williams R eds). 105-128 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiroki Takahashi: "The Japanese animal models of autoimmune hepatitis" Molecular Basis of Autoimmune Hepatitis (MoFarlane IG,williams R eds). 165-176 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Han K-K, et al: "Occurrence of antibody against rat Iepatic endothelial cells in patients with autoimmune Iepatitis." Dig. Dis. Sci. 40. 1213-1220 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Zeniya M et al.: "Thrombomodulin expression of sinusordal and othelial cells in chronic Iepatitis." J. Gastroenterol. Hepatol.10. S77-S80 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ikeda Y et al.: "Crossreactivity of anti-aulfatide-antibody with aulfated glycosaminoglycans and DNA in sera from patieuts with sutormmurnd Iepatitis." Int. Hepatol. Comm.(in press).

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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