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Molecular mechanisms of vascular injury in an autoantibody-induced model of granulomatous arteritis

Research Project

Project/Area Number 15591504
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKinki University

Principal Investigator

SAGA Toshihiko  Kinki University, School of Medicine, Professor, 医学部, 教授 (30153927)

Co-Investigator(Kenkyū-buntansha) MIYAZAWA Masaaki  Kinki University, School of Medicine, Professor, 医学部, 教授 (60167757)
TABATA Nobutada  Kinki University, School of Medicine, Assistant Professor, 医学部, 講師 (40298948)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsarteritis / mouse model / autoantibody / hybridoma / granuloma / immune complex / Fc receptor / complement
Research Abstract

MRL/MpJ-lpr/lpr (MRL/lpr) mice spontaneously develop immune complex-mediated glomerulonephritis, granulomatous arteritis, chronic destructive arthritis, and thrombocytopenia Recent genetic analyses in a variety of lupus-prone strains have pointed out a close correlation between autoantibodies reactive with the endogenous retroviral env gene product, gp70, and the development and severity of glomerulonephritis. We have previously shown that a high proportion of anti-gp70 antibody-producing hybridoma clones established from MRL/lpr mice induce proliferative or wire loop-like glomerular pathology with massive granular depositions of gp70, IgG and C3 in affected glomeruli when transplanted into syngeneic non-autoimmune or severe combined immunodeficiency mice.
We found here that repeated intravenous injections of purified monoclonal anti-gp70 autoantibodies induced glomerular pathology associated with gp70 deposition. Further, the above injections of the anti-gp70 antibody purified from clone 12H5.1 also induced granulomatous arteritis of the lungs in a half of the injected (BALB/c×MRL)F_1 and (C57BL/6×MRL)F_1 strains of mice.
To evaluate the possible roles of Fc receptor-expressing cells and complements, common FcRγ-chain-knockout FcγRIIb-knowckout, and C3-knockout strains on the C57BL/6 background were mated with MRL mice, and F_2 progenies possessing the each homozygous knockout genotype were selected. Purified antui-gp70 monoclonal antibody 12H5.1 was injected repeatedly into the F_2 mice, and the development of granulomatous arteritis was evaluated histopathologically. The results indicated that the formation of circulating immune complexes was involved in the development of the antibody-induced arteritis.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (29 results)

All 2005 2004 2003 Other

All Journal Article (16 results) Book (9 results) Patent(Industrial Property Rights) (2 results) Publications (2 results)

  • [Journal Article] Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians.2005

    • Author(s)
      Kanari, Y., M.Clerici, H.Abe, H.Kawabata, D.Trabattoni, S.Lo Caputo, F.Mazzotta, H.Fujisawa, A.Niwa, C.Ishihara, Y.A.Takei, M.Miyazawa
    • Journal Title

      AIDS (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Both T and non-T cells with proliferating potentials are effective in inducing suppression of allograft responses by alloantigen-specific intravenous presensitization combined with suboptimal doses of 15-deoxyspergualin2004

    • Author(s)
      Tahara H., N.Iwanami, N.Tabata, H.Matsumura, T.Matsuura, T.Kurita, M.Miyazawa
    • Journal Title

      Transplant.Immunol. 13

      Pages: 25-32

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Identification of a protective CD4^+ T-cell epitope in p15^<gag> of Friend murine leukemia virus and role of the MA protein targeting the plasma membrane in immunogenicity2004

    • Author(s)
      Sugahara, D., S.Tsuji-Kawahara, M.Miyazawa
    • Journal Title

      J.Virol. 78

      Pages: 6322-6334

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Cytotoxic T lymphocyte-based control simian immunodeficiency virus replication in a preclinical AIDS vaccine trial2004

    • Author(s)
      Matano, T., M.Kobayashi, H.Igarashi, A.Takeda, H.Nakamura, M.Kano, C.Sugimoto, K.Mori, A.Iida, T.Hirata, M.Hasegawa, T.Yuasa, M.Miyazawa, Y.Takahashi, M.Yasunami, A.Kimura, D.H.O'Connor, D.I.Watkins, Y.Nagai
    • Journal Title

      J.Exp.Med. 199

      Pages: 1709-1718

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Host genes that influence immune and non-immune resistance mechanisms against retrovrial infections2004

    • Author(s)
      Miyazawa, M
    • Journal Title

      Recent Res.Devel.Virol. 6

      Pages: 105-118

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Host genes that influence immune and non-immune resistance mechanisms against retrovrial infections.2004

    • Author(s)
      Miyazawa, M.
    • Journal Title

      Recent Res.Devel.Virol. 6

      Pages: 105-118

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial.2004

    • Author(s)
      Matano, T., M.Kobayashi, H.Igarashi, A.Takeda, H.Nakamura, M.Kano, C.Sugimoto, K.Mori, A.Iida, T.Hirata, M.Hasegawa, T.Yuasa, M.Miyazawa Y.Takahashi, M.Yasunami, A.Kimura, D.H.O'Connor, D.I.Watkins, Y.Nagai.
    • Journal Title

      J.Exp.Med. 199

      Pages: 1709-1718

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of a protective CD4+ T-cell epitope in p15gag of Friend murine leukemia virus and role of the MA protein targeting to tie plasma membrane in immunogenicity.2004

    • Author(s)
      Sugahara, D., S.Tsuji-Kawahara, M.Miyazawa
    • Journal Title

      J.Virol. 78

      Pages: 6322-6334

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Both T and non-T cells with proliferating potentials are effective in inducing suppression of allograft responses by alloantigen-specific intravenous presensitization combined with suboptimal doses of 15-deoxyspergualin.2004

    • Author(s)
      Tahara H., N.Iwanami, N.Tabata, H.Matsumura, T.Matsuura, T.Kurita, M.Miyazawa
    • Journal Title

      Transplant.Immunol. 13

      Pages: 25-32

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial2004

    • Author(s)
      Matano, T., M.Kobayashi, H.Igarashi, A.Takeda, H.Nakamura, M.Kano, C.Sugimoto, K.Mori, A.Iida, T.Hirata, M.Hasegawa, T.Yuasa, M.Miyazawa, Y.Takahashi, M.Yasunami, A.Kimura, D.H.O'Connor, D.I.Watkins, Y.Nagai
    • Journal Title

      J.Exp.Med. 199

      Pages: 1709-1718

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Williams syndrome associated with complete atrioventricular septal defect2003

    • Author(s)
      Nakamoto, S., T.Saga, T.Shinohara
    • Journal Title

      Heart 89

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Successful surgical treatment of mitral regurgitation for complete rupture of the anterior papillary muscle after acute myocardial infarction2003

    • Author(s)
      Inoue, T., J.Iemura, T.Saga
    • Journal Title

      Jap.J.Thorac.Cardiovasc.Surg. 52

      Pages: 565-568

    • NAID

      50000321148

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Obstructed coarctation of a right aortic arch in an adult female2003

    • Author(s)
      Kaneda, T., S.Miyake, T.Kubo, T.Ogawa, T.Inoue, T.Matsumoto, M.Onoe, S.Nakamoto, H.Kitayama, T.Saga
    • Journal Title

      Thorac.Cardiovasc.Surg. 51

      Pages: 350-352

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Williams syndrome associated with complete atrioventricular septal defect.2003

    • Author(s)
      Nakamoto, S., T.Saga., T.Shinohara
    • Journal Title

      Heart 89

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Successful surgical treatment of mitral regurgitation for complete rupture of the anterior papillary muscle after acute myocardial infarction.2003

    • Author(s)
      Inoue, T., J.Iemura, T.Saga.
    • Journal Title

      Jap.J.Thorac.Cardiovasc.Surg. 51

      Pages: 565-568

    • NAID

      50000321148

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Obstructed coarctation in a right aortic arch in an adult female.2003

    • Author(s)
      Kaneda, T., T.Miyake, T.Kudoh, T.Ogawa, T.Inoue, T.Matsumoto, M.Onoe, S.Nakamoto, H.Kitayama, T.Saga.
    • Journal Title

      Thoracic Cardiovasc.Surg. 51

      Pages: 350-352

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 冠動脈外科の要点と盲点(竹内 靖夫編集)2005

    • Author(s)
      佐賀 俊彦
    • Publisher
      (株)文光堂(東京)(印刷中)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 日本臨床 2005年増刊 臨床免疫学(下)(山本一彦編集)2005

    • Author(s)
      宮澤 正顯
    • Publisher
      日本臨床社(大阪)(印刷中)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 冠動脈外科の要点と盲点(竹内 靖夫:編集)2005

    • Author(s)
      佐賀 俊彦
    • Publisher
      (株)文光堂 (東京)(印刷中)
    • Related Report
      2004 Annual Research Report
  • [Book] 日本臨床 2005年増刊 臨床免疫学(下)(山本一彦:編集)2005

    • Author(s)
      宮澤 正顯
    • Publisher
      日本臨床社(大阪)(印刷中)
    • Related Report
      2004 Annual Research Report
  • [Book] From Animal Models to Human Genetics : Research on the Induction and Pathogenicity of Autoantibodies(K.Conrad, et al., editors)2004

    • Author(s)
      Miyazawa, M., E.Kajiwara, N.Tabata, T.Ogawa, T.Yuasa, H.Matsumura
    • Total Pages
      611
    • Publisher
      Pabst Science Publishers, Lengerich
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 心疾患の手術適応と至適時期(赤阪 隆史, 他編集)2004

    • Author(s)
      佐賀 俊彦, 篠原 徹
    • Total Pages
      400
    • Publisher
      (株)文光堂(東京)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Pathogenicity of autoantibodies reactive with the endogenous retroviral envelope glycoprotein gp70. In From Animal Models to Human Genetics : Research on the Induction and Pathogenicity of Autoantibodies (K.Conrad, et al. editors).2004

    • Author(s)
      Miyazawa, M., E.Kajiwara, N.Tabata, T.Ogawa, T.Yuasa, H.Matsumura
    • Publisher
      Pabst Science Publishers, Lengerich
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] From Animal Models to Human Genetics : Research on the Induction and Pathogenicity of Autoantibodies (K. Conrad, et al., editors)2004

    • Author(s)
      Miyazawa, M., E.Kajiwara, N.Tabata, T.Ogawa, T.Yuasa, H.Matsumura
    • Total Pages
      611
    • Publisher
      Pabst Science Publishers, Lengerich
    • Related Report
      2004 Annual Research Report
  • [Book] 心疾患の手術適応と至適時期(赤阪 隆史、他:編集)2004

    • Author(s)
      佐賀 俊彦, 篠原 徹
    • Total Pages
      400
    • Publisher
      (株)文光堂 (東京)
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規ヒト内在性レトロウイルスHC2のenv遺伝子2004

    • Inventor(s)
      宮澤 正顯, 阿部 弘之
    • Industrial Property Rights Holder
      (財)大阪産業振興機構
    • Industrial Property Number
      2004-231412
    • Filing Date
      2004-08-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 新規ヒト内在性レトロウイルスHC2のenv遺伝子2004

    • Inventor(s)
      宮澤正顯, 阿部弘之
    • Industrial Property Rights Holder
      (財)大阪産業振興機構
    • Industrial Property Number
      2004-231412
    • Filing Date
      2004-08-05
    • Related Report
      2004 Annual Research Report
  • [Publications] Sugahara, D., S.Tsuji-Kawahara, M.Miyazawa: "Identification of a protective CD4^+T-cell epitope in the p15^<gag> of Friend murine leukemia virus and the role of the MA protein targeting to the plasma membrane for its immunogenicity."Journal of Virology. 印刷中. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tahara, H., Iwanami, N.Tabata, H.Matsumura, T.Matsuura, T.Kurita, M.Miyazawa: "Both T and non-T cells with proliferating potentials are effective in inducing suppression of allograft responses by alloantigen-specific intravenous presensitization combined with suboptimal doses of 15-deoxyspergualin."Transplant Immunology. 印刷中. (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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