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1992 Fiscal Year Final Research Report Summary

HIGH MOLECULAR PROTEINS RESPONSIBLE FOR INTRACTABLE INFLAMMATORY DISEASES-IDENTIFICATION AND GENE EXPRESSION-

Research Project

Project/Area Number 02454166
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

NOSE Masato  TOHOKU UNIV. SCHOOL OF MEDICINE, ASST.PROF., 医学部, 助教授 (70030913)

Co-Investigator(Kenkyū-buntansha) KUDOH Toshio  TOHOKU UNIV. RES. INST. FOR TUBERCULOSIS AND CANCER, ASST.PROF., 拡酸菌研究所, 助教授 (70091684)
YAMAMOTO Tokuo  TOHOKU UNIV. GENE RESEARCH CENTER, PROF., 遺伝子実験施設, 教授 (30192412)
Project Period (FY) 1990 – 1992
KeywordsCollagen disease / Autoimmune disease / Glomerulonephritis / Arteritis / Nephritogenic antibody genes / TNF / RFLP / Background genes
Research Abstract

It is still unclear what functional molecules are critical for the development of intractable inflammatory diseases including collagen disease, although several parameters of autoimmunity have been pointed out in these diseases. This project was performed to identify high molecular proteins responsible for the development of collagen disease and to analyze their gene expression by using a murine model, MRL/Mp-lpr/lpr (MRL/lpr) mice. This strain of mice spontaneously develops a lethal glomerulonephritis, arteritis and arthritis, associated with the expression of the immunological disorder-inducing gene, lpr, which is recently clarified to be Fas antigen deletion mutant. These mice develop all of these diseases in the same individual, but MRL genetic background is required for them in addition to the lpr gene.
We clarified that the background genes for these diseases are able to be genetically segregated each other by using the MRL hybrid mice with non-autoimmune-prone mice. Considering t … More he facts from these MRL hybrid mice, we identified the responsible proteins for collagen disease in MRL/lpr mice; IgG3 subclass for glomerulonephritis and TNF for granulomatous arteritis.
In further analyses of IgG3, we succeeded in obtaining nephritogenic IgG3 producing clones against normal or SCID mice, and moreover these clone generated regular variations of lupus nephritis in histopathological manifestations. Immunoglobulin gene analysis of these clones clarified that each nephritogenic IgG3 is derived from a different B cell precursor and used a different VH germline gene. Moreover, one of these IgG3 was not associated with somatic mutation in the VH region, indicating that somatic mutation in the VH region is not required for the development of nephritogenic antibody. Furthermore, this germline VH gene was identical to that found in a non-autoimmune-prone mice. Thus, there may be no autoimmune-prone specific al- lelism in the germline VH gene relevant to the nephritogenic antibody.
Regarding TNF on the development of arteritis, there is no RFLP of TNF-exon 4 among MRL and non- autoimmune-prone mice. However, it was clear that the individuals with arteritis among the MRL hybrid mice manifest a positive correlation between TNF and IL-1 beta mRNA level, but not between other macrophage-related cytokine mRNA such as LIF, M-CSF and Eta-1. This fact indicates that particular potential of macrophages are required for the development of arteritis in MRL/lpr mice, restricted with their background genes.
Further studies of the sequences in the variable regions of IgG3 responsible for the nephritogenicity, including the association of the constant regions, and the induction mechanisms of nephritogenic antibody- producing B cell clones are required. An arteritis-prone strain of mice established from the MRL hybrid mice will be useful for further studies of the genetic basis of arteritis and of the responsible genes. Less

  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Wiersma,E.,etul.: "Evidence of IgG-mediated enhancement of the antibody response in vivo without complement activation....." Eur.J.Immunol.20. 2585-2589 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nose,M.,etal.: "Inhibition of processing of asparagine-linked corbo-hydrate chains on IgG2a by using swainsonine....." J.Immunol.145. 910-914 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nose,M.,etal.: "Recombinant Fc of human IgG1 prepared in an Escherichia coli system escapes reccgnition by macrophages" Int.Immunol.2. 1109-1112 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nose,M.,etal.: "Tissue distribution of HRF20,a novel factor preventing the membrane atlack of homologons complement,and....." Immunology. 70. 145-149 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miquochi,T.,etal.: "Structural changes in the cligosaccharide chains of IgG in antoimmune MRL/Mp-lpr/lpr mice" J.Immunol.145. 1794-1798 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuda,H.,etal.: "Proton nuclear magnetic resonance studies of the structure of the Fc fragment of human immunoglobulin G1" Mol.Immunol. 27. 571-579 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi,S.,etal.: "IgG3 production in MRL/lpr mice is responsible for develop-ment of lups nephritis" J.Immunol.147. 515-519 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masuda,T,et al.: "Expansion of the population of double neqative CD4~8~Tαβ col in the liver is a common feature of autoimmune mice" J.Immunol.147. 2907-2912 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Itoh,J.,etal.: "Pathopenic significamce of serum components in the development of autoimmune polyarteritis in MRL/Mp mice....." Am.J.Pathol.139. 511-522 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Itoh,J.,etal.: "Expression of decay-accelerating factor is reduced on hyperplastic synovial lining calls in rheumatoid synovitis" Clin.Exp.Immunol.83. 364-368 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hyun,B.H.,etal.: "A new mouse strain manifesting high proteinuria and kidney glomerular defect" Lab.Animal Science. 41. 442-446 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanno,H.eatl.: "Spontaneous development of pancreatitis in the MRL/Mp strain of nice in autoimnure mechanism" Clin.Exp.Immunol.89. 68-73 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Itoh,J.,etal.: "Application of two-cdor immunofluorescence staiming to demonstration of T-cells and HLA-DR-bearing cells....." J.Histochem.Cytochem.40. 1675-1683 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kusakari,C.,etal.: "IgA1 localiqation in tonsillar follicular dendritic cells is charactenistic of IgA nephropathy" Adv.Otorhinolaryngol.47. 222-226 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohsaki,H.,etal.: "Hypersensitivity angites in an adult with rubella infection" J.Rheumatol.19. 1160-1161 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi,S.,eatl: "Cloning and cDNA sequence analysis of nephritogenic monoclonal antibcdies derived from an MRL/lpr lupus mouse" Mol.Immunol.30. 177-182 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢 眞人 他: "MRLマウス概説ー自己免疫病の分子的理解の手ががりー" 蛋白核酸酸素. 35. 67-72 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高橋 智 他: "MRL/lprマウス動脈炎におけるマクロファージの関与" 臨床免疫. 22. 1288-1295 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 村上 一宏 他: "膠原病における微小循環障害の病理学的・免疫学的孝察" 治療学. 26. 30-35 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢 眞人: "IgG-Fc部の糖鎖とマクロファージFcレセプター" 臨床免疫. 24. 196-206 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢 眞人: "動脈炎自然発症モデルマウスMRL/lprー動脈炎発症における免疫異常誘導遺伝子と背景遺伝子" 現代医療. 24. 126-129 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅野 祐幸 他: "マクロファージとサイトカインー組織傷害とその制御ー" 免疫薬理. 11. 23-28 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] TaKahashi,M.,etal(分担): "Moleculor Approaches to the Study and Treatment of Human Diseases" Elsevier Science,Amsterdam, 455 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nose,M.(分担): "Intractable Vasculitis Syndromes" Hokkaido Univ.Press,Sapporo, 284 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢 眞人 他(分担): "血管壁細胞の対能とその制御材構" 共立出版, 300 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢 眞人 他(分担): "新生化学実験講座12(II)" 東京化学同人, 405 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢 眞人(分担): "医学のあゆみ:腎疾患" 医歯葉出版,東京, 366 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢 眞人 他(分担): "自己免疫とトレランス" 中外医学社,東京, 249 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢 眞人,他(分担): "分十病理学" 文光堂,東京, (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢 眞人,他(分担): "グリコバイオロジー第6巻:グリコパソロジー" 講談社,東京, (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wiersma, E., Nose, M., and Heyman, B.: "Evidence of IgG-mediated enhancement of the antibody response in vivo without complement activation via the classical pathway." Eur. J. Immunol.20. 2585-2589 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nose, M. and Heyman, B.: "Inhibition of processing of asparagine-linked carbohydrate chains on IgG2a by using swainsonine has no influence upon antibody effector functions in vitro." J. Immunol.145. 910-914 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nose, M.: "Significance of genetic background of collagen disease in elucidating the gap between pathological features and immunological disorders." Connect. Tissue. 21. 163-173 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nose, M., Takano, R., Nakamura, S., Arata, Y., and Kyogoku, M.: "Recombinant Fc of human IgG1 prepared in an Escherichia coli system escapes recognition by macrophages." Int. Immunol.2. 1109-1112 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nose, M., Kato, M., Okada, N., Kyogoku, M., and Okada, H.: "Tissue distribution of HRF20, a novel factor preventing the membrane attack of homologous complement, and its predominant expression on endothelial cells in vivo." Immunology. 70. 145-149 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mizuochi, T., Hamako, J., Nose, M., and Titani, K.: "Structural changes in the oligosaccharide chains of IgG in autoimmune MRL/Mp-lpr/lpr mice." J. Immunol.145. 1794-1798 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuda, H., Nakamura, S., Ichikawa, Y., Kozai, K., Takano, R., Nose, M., Endo, S., Nishimura, Y., and Arata, Y.: "Proton nuclear magnetic resonance studies of the structure of the Fc fragment of human immunoglobulin G1: Comparisons of native and recombinant proteins." Mol. Immunol.27. 571-579 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, S., Nose, M., Sasaki, J., Yamamoto, T., and Kyogoku, M.: "IgG3 production in MRL/lpr mice is responsible for development of lupus nephritis." J. Immunol.147. 515-519 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masuda, T., Ohteki, T., Abo, T., Seki, S., Nose, M., Nagura, H., and Kumagai, K.: "Expansion of the population of double negative CD4-8- T-alpha--beta-cell in the liver is a common feature of autoimmune mice." J. Immunol.147. 2907-2912 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Itoh, J., Nose, M., and Kyogoku, M.: "Pathogenic significance of serum components in the development of autoimmune polyarteritis in MRL/Mp mice bearing the lymphoproliferation gene." Am. J. Pathol.139. 511-522 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Itoh, J., Nose, M., Fujita, T., Kato, M., Ohyama, A., and Kyogoku, M.: "Expression of decay-accelerating factor is reduced on hyperplastic synovial lining cells in rheumatoid synovitis." Clin. Exp. Immunol.83. 364-368 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hyun, B. H., Wakasugi, N., Nose, M., Saito, T., and Tomita, T.: "A new mouse strain manifesting high proteinuria and kidney glomerular defect." Lab. Animal Science. 41. 442-446 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, M., Nose, M., Itoh, J., Sasaki, J., Yamamoto, T., and Kyogoku, M.: "Significance of IgG3 production on the developmental mechanisms of glomerulonephritis in MRL/lpr autoimmune disease mice." Molecular Approaches to the Study and Treatment of Human Diseases. T.O. Yoshida and J.M. Wilson, eds. (Amsterdam: Elsevier Science). 145-149 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohsaki, H., Sasaki, T., Hatakeyama, A., Nose, M., and Yoshinaga, K.: "Hypersensitivity angitis in an adult with rubella infection." J. Rheumatol.19. 1160-1161 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mori, S., Nose, M., Miyazawa, M., Kyogoku, M., Wolfinbarger, J.B., and Bloom, M.E.: "Identification of the cells infected with Aleutian mink disease parvovirus (ADV): Role of follicular dendritic cells in the pathogenesis of Aleutian mink disease." Dendritic Cells. 1. 11-16 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kusakari, C., Takasaka, T., Nose, M., and Kyogoku, M.: "IgA1 localization in tonsillar follicular dendritic cells is characteristic of IgA nephropathy." Adv. Otorhinolaryngol.47. 222-226 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanno, H., Nose, M., Itoh, J., Taniguchi, Y., and Kyogoku, M.: "Spontaneous development of pancreatitis in the MRL/Mp strain of mice in autoimmune mechanism." Clin. Exp. Immunol.89. 68-73 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Itoh, J., Kinjoh, K., Ohyama, A., Nose, M., and Kyogoku, M.: "Application of two-color immunofluorescence staining to demonstration of T-cells and HLA-DR-bearing cells in rheumatoid synovitis." J. Histochem. Cytochem.40. 1675-1683 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ezura, M., Fujiwara, S., Nose, M., Yoshimoto, T., and Kyogoku, M.: "Attempts to induce immune-mediated cerebral arterial injury for an experimental model of moyamoya disease." Child's Nerv. Syst.8. 263-267 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, S., Itoh, J., Nose, M., Ono, M., Yamamoto, T., and Kyogoku, M.: "Cloning and cDNA sequence analysis of nephritogenic monoclonal antibodies derived from an MRL/lpr lupus mouse." Mol. Immunol.30. 177-182 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nose, M.: "Genetic basis of vasculitis in lupus nephritis." Intractable Vasculitis Syndromes. T. Tanabe, ed. (Sapporo, Hokkaido Univ. Press). 145-153 (1993)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1994-03-24  

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