2004 Fiscal Year Final Research Report Summary
Molecular mechanisms of vascular injury in an autoantibody-induced model of granulomatous arteritis
| Project/Area Number |
15591504
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Kinki University |
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Principal Investigator |
SAGA Toshihiko Kinki University, School of Medicine, Professor, 医学部, 教授 (30153927)
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| 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)
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| Project Period (FY) |
2003 – 2004
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| Keywords | arteritis / mouse model / autoantibody / hybridoma / granuloma / immune complex / Fc receptor / complement |
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| 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.
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[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
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[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
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Journal Title
J.Exp.Med. 199
Pages: 1709-1718
Description
「研究成果報告書概要(和文)」より
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[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.
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Journal Title
J.Exp.Med. 199
Pages: 1709-1718
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
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Pages: 350-352
Description
「研究成果報告書概要(和文)」より
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[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.
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Journal Title
Thoracic Cardiovasc.Surg. 51
Pages: 350-352
Description
「研究成果報告書概要(欧文)」より
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