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Animal model for severe alcoholic hepatitis by chronic ethanol feeding and immunization with fusions of dendritic cells and acetaldehyde adducts.

Research Project

Project/Area Number 11670538
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SAITO Saburo (2001)  JIKEI UNIVERSITY SCHOOL OF MEDICINE , DEPARTMENT OF MOLECULAR IMMUNOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (10186934)

山内 眞義 (1999-2000)  東京慈恵会医科大学, 医学部, 助教授 (20138811)

Co-Investigator(Kenkyū-buntansha) SHIMADA Seika  JIKEI UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, RESEARCH ASSISTANT, 医学部, 助手 (90297391)
INOUE Takahiro  JIKEI UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, RESEARCHASSISTANT, 医学部, 助手 (60256336)
斉藤 三郎 (斎藤 三郎)  東京慈恵会医科大学, 医学部, 講師 (10186934)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsSevere alcoholic hepatitis / Acetaldehyde adduct / Dendritic cells / Alcoholic liver damage
Research Abstract

(1) Mouse albumin-acetalciehyde adduct (ADT) was prepared with the reducing agent according to the method of Israel et al (Proc Nati Acad Sci USA 83 : 7923,1986).
(2) In order to choose the mouse that responds to ADT well, four species of mice (B10S, BALB/C, C3H, and B6 mouse) with different strains were prepared. Mice were immunized with ADT. The lymphocytes were obtained from the systemic lymph node of each mouse, and in vitro lymphocyte stimulation test was performed. The stimulation index was remarkably higher in B6 mice than in any other mice.
(3) B6 mice were divided into 6 groups with or without immunization and ethanol feeding (10 weeks). The stimulation index of ^3H-thymidine uptake into lymphocytes cultured with mouse albumin or ADT was measured, The stimulation .index was increased remarkably in ethanol-fed mice immunized with ADT. However, no elevation in plasma AST and ALT levels was observed.,and neither inflammatory cell infiltration nor hepatic necrosis was observed in the liver.
(4) As immune response was induced in the lymphocyte in this model, we are trying to isolate T cells from the lymphnode, and inject T cells into portal or systemic vein to investigate the induction of immune response and liver damage. We also made fusions of dendritic cells and ADT. We are trying to make a model for alcoholic hepatitis by chronic ethanol feeding and immunization with this fusion cells.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (5 results)

All Other

All Publications (5 results)

  • [Publications] 島田青佳, 他: "慢性エタノール投与マウスに対するアセトアルデヒドアダクトによる細胞性免疫の誘導と肝障害"アルコールと医学生物学. 21. 85-91 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimada S, et al.: "Experimental studies on the relationship between immune responses and liver damage induced by ethanol after immunization with homologous acetaldehyde adducts"Alcohol Clin Exp Res. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Seika Shimada, Masayoshi Yamauchi, Masashi Takamatsu, Shinichiro Uetake, Mitsuru Ohata, Gotaro Toda, Saburo Saito: "Experimental studies on the relationship between immune responses and liver damage induced by ethanol after immunization with homologous acetaldehyde adducts."Alcohol and Biomedical Research. 21. 85-91 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 島田青佳, 他: "慢性エタノール投与マウスに対するアセトアルデヒドアダクトによる細胞性免疫の誘導と肝障害"アルコールと医学生物学. 21. 85-91 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimada S, et al: "Experimental stndies on,the relationship between immune responses and liver dame Induced by ethanol after immunization with homologons acetcldehyde adducts"Alcohol Clin Exp Res. (in press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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