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1990 Fiscal Year Final Research Report Summary

Analysis of the Mechanism of Renal Injury by Application of Monoclonal Antibodies.

Research Project

Project/Area Number 01480163
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionNiigata University

Principal Investigator

SHIMIZU Fujio  Niigata University School of Medicine, Professor, 医学部, 教授 (40012728)

Co-Investigator(Kenkyū-buntansha) MORIOKA Tetsuo  Niigata University School of Medicine, Assistant, 医学部, 助手 (00210146)
OITE Takashi  Niigata University School of Medicine, Associate professor, 医学部, 助教授 (60018744)
Project Period (FY) 1989 – 1990
KeywordsMonoclonal Antibody / Proteinuria / Glomerular Epithelial Cell / Mesangium / Mesangiolysis / Cultured Cell
Research Abstract

The purpose of this study is to analyze the mechanism of renal injury at the molecular level by application of monoclonal antibody (MA). We have produced 2 kinds of MAs which induce a massive proteinuria in rats by a single intravenous injection. MA 5-1-6, IgG1, binds to the surface of glomerular epithelial foot processes, mainly to slit diaphragm MA 1-22-3, IgG3, binds to the limited surface of mesangial cells facing endothelial cells. The minimum dose of both MAs required to induce proteinuria is very small in comparison with already reported one in several kinds of experimental glomerulonephritides. This also indicates that each epitope recognized by both MAs is a very limited point which plays the critical role in keeping the normal glomerular permeability.
The study of our MAs indicates that a chain reaction leading to proteinuria with or without mesangial lesions is initiated by the reaction between 2 defined molecules (MA and very specific surface molecules of glomerular cells). In the case of MA 5-1-6 the proteinuria is induced without the involvement of the classical mediators of immune injury such as complement or leukocytes.
We have demonstrated that glomerular cell injury depends on an epitope specific interaction between a cell surface epitope as a receptor and a MA as a ligand. This seems to be an entirely new mechanism by which proteinuria can be induced. The simplicity of MA-induced in vivo models is ideal for analyzing the immunopathology of induced lesions at molecular levels.

  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Kawachi,H.;Shimizu,F.: "Quantitative study of proteinuria inducing monoclonal antibody 5ー1ー6." Kidney Int.35. 351 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oite,T.;Shimizu,F.: "Hatenーspecific celluar immune response producing glomerular injury." Clin.exp.Immunol.76. 463-468 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Howie,A.J.;Shimizu,F.: "Different types of sclerosing glomerular lesions in six experimental models of proteinuria." J. Pathol.157. 141-151 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水 不二雄: "分子レベルにおける腎障害機序解析の最前線 ーモノクロ-ナル抗体はどこまで有用かー" 医学のあゆみ. 152. 595 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimizu,F.: "Kinetics of injected proteinuriaーinducing monoclonal antibody and its recognized antigen in rats." J. Am. Soc. Nephrol.1. 539 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okasora,T.;Shimizu,F.: "Altered localization of antigen recognized by proteinuriaーinducing monoclonal antibody in experimental nephrosis." J. Am. Soc. Nephrol.1. 539 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清水 圧二雄(分担執筆): "臨床腎蔵病学" 朝倉書店, 584 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimzu,F.(contributor): "Structural basis for glomerular dysfunction" Nishimura Co. Ltd., (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Howie, A. J: "Shimizu, F. Different types of sclerosing glomerular lesions in six experimental models of proteinuria." J. Pathol.157. 141 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawachi, H. --: "Shimizu, F. Quantitative study of proteinuria inducing monoclonal antibody 5-1-6." Kidney Int.35,. 351 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] OITE, T. --: "Shimizu, F. Hapten-specific cellular immune response producing glomerular injury." Clin. exp. Immunol.,. 76,. 463, (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kagami, S.: "Shimizu, F. Mechanism of formation of subepithelial electron dense deposits in active in situ immune complex glomerulonephritis." Am. J. Pathol.136. 631 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawachi, H.: "Shimizu, F. Induction of proteinuria and morphological changes in the rat by a monoclonal antibody against mesangial cell surface." Kidney Int.,. 37,. 418 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuyama, M.: "Shimizu, F. Genetic regulation of the development of glomerular sclerotic lesions in the BUF/Mna rat." Nephron. 54. 334 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu, F.: "Kinetics of injected proteinuria-inducing monoclonal antibody and its recognized antigen in rats." J. Am. Soc. Nephrol.1. 539 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu, F.: "Effects of traditional Chinese medicine on exeperimental nephrosis in rats. In proceedings of the joint meeting 11th international congress of nephrology." Kanebo Pharmaceutical Co Ltd. 17. (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Moritaka, T: "Shimizu, F : Production by cultured human monocytes of mesangial cell proliferation factor(s) differing from IL-1 and IL-6" Clin. exp. Immunol.83. 182 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okasora, T.: "Shimizu, F. Altered localization of antigen recognized by proteinuria-inducing monoclonal antibody in experimental nephrosis." Virchows Archiv B cell pathol.60. 41 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato, T.: "Shimizu, F. Nephrotoxic serum nephritis in nude rats : the roles of host immune reactions." Clin. exp. Immunol.84.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Narita, I.: "Shimizu, F. Monocytes secrete factors regulating GAG synthesis in mesangial cells in vitro." Clin. exp. Immunol.84.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu, F.: "Analysis of the mechanism of renal injury at molecular levels by application of monoclonal antibodies." proceedings of the IVth Asian Pacific congress of nephrology.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu, F.: Nishimura Co. Ltd.New concepts of glomerular injury : role of an epitope specific interaction. In structural basis for glomerular dysfunction.,

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu, F.: Springer-Verlag,. Cell and matrix in monoclonal antibody-induced mesangiolysis. In proceedings of the XIth international congress of nephrology.,

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

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Published: 1993-08-12  

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