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INDUCTION OF AUTOIMMUNE-TYPE LIVER INJURY IN MICE BY THE ANTI-IDEOTYPIC ANTIBODY TO THE ANTI-ASIALOGLYCOPROTEIN RECEPTOR ANTIBODY.

Research Project

Project/Area Number 03670363
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

MIZUNO Motoo  OKAYAMA UNIVERSITY HOSPITAL ATTACHED TO MEDICAL SCHOOL, ASSISTANTS, 医学部附属病院, 助手 (90221605)

Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsMonoclonal antibody / Anti-ideotypic antibody / Hepatocyte membrane / Asialoglycoprotein receptor / Autoimmune-type liver injury / モノグロナール抗体 / アシアログリコプロティンレセプター / モノクロナ-ル抗体
Research Abstract

1.Analysis of 8D7 monoclonal antibody (MoAb).
8D7 monoclonal antibody (MoAb) was shown to react with affinity-purified human asialoglycoprotein receptors (ASGPR) in an ELISA. Distributions of ASGPR in human hepatocellular carcinoma (HCC) was studied immunohistochemically. ASGPR was distributed diffusely on the plasma membrane in the well differentiated HCC. In contrast, the surface expression of ASGPR was lost in poorly differentiated HCC. Various alterations of the expression of ASGPR closely related to differentiation and proliferative activity of the tumor cells were shown in HCC.
2.Production of anti-ideotypic antibodies to the 8D7 anti-ASGPR MoAb.
BALB/c mice were immunized with 8D7 MoAb, and a syngenetic anti-ideotypic (anti-Id) MoAb, 3C8, an IgMkappa, was generated. 3C8 MoAb bound to 8D7 MoAb in an membrane constituents in an ELISA. The liver membrane constituents inhibited 8D7 MoAb binding to 3C8 MoAb in an ELISA. Immunohistochemical staining of the plasma membrane of rat hepatocytes by 8D7 MoAb was inhibited by the 3C8 anti-Id MoAb.
BALB/c mice were immunized with 3C8 anti-Id MoAb, and anti-anti-Id MoAbs which reacted with the liver membrane constituents could be generated. These results suggest that 3C8 anti-Id MoAb recognizes paratope of 8D7 anti-ASGPR MoAb and includes "internal images".
3.Induction of autoimmune-type liver injury by 3C8 anti-Id MoAb.
Thymectomy of BALB/c mice was performed 3 days after birth, and thymectomized mice were immunized with 3C8 anti-Id MoAb. This experiment is currently on going.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] 山田 剛太郎: "肝臓組織の免疫電顕" 細胞. 23. 430-433 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] M.MIZUNO: "Ultrastructural immunocytochemical observations of rat and human hepatocyte plasma membrane antigens." J.Clin.Electron Microscopy. 24. 463-464 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 水野 元夫: "原発性胆汁性肝硬変における胆管病変の免疫組織学的検討" 肝臓. 32. 1190-1191 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 水野 元夫: "B型肝炎、成立をめぐって" 第23回日本医学会総会会誌III. III. 92 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] I.Hyodo: "Distribution ofasialoglycoprotein receptor in human hepatocellular carcinoma." Liver. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 水野 元夫: "アシアロ糖蛋白レセプターと自己免疫性肝炎-抗アシアロ糖蛋白レセプター抗体の診断的意義-" 肝胆膵. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] M.MIZUNO: "Frontiers of Mucosal Immunology.Vol.2 M.Tsuchiya,H.Nagura,T.Hibi and I.Moro.edt." EXCEPTA MEDICA,Amsterdam, 660 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] M.Mizuno, et al.: "Ultrastructural immunocytochemical observations of rat and human hepatocyte plasma membrane antigens." J.Clin.Electron Microscopy. 24. 463-464 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] M.Mizuno, et al.: "Immunohistochemical study of lymphocytes infiltrating to bile duct epithelia in primary biliary cirrhosis." Frontiers of Mucosal Immunology M.Tsuchiya, et al.edt.Vol 2. 95-98 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] I.Hyodo, et al.: "Distribution of asialoglycoprotein receptor in human hepatocellular carcinoma." Liver. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hyodo I: "Distribution of asiuloglycopvotein receptor in human hepatocellular carcinona." Liver. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 水野 元夫: "アシアロ糖蛋白レセプターと自己免疫性肝炎 -抗アシアロ糖蛋白レセプター抗体の診断町意義-" 肝胆膵. 26. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mizuno M: "Immundistochemical study of adhesion molecules in chronic hepatitis" J.Clin Electron Microsiory. (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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