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Research on The Role of Complement Regulatory Membrane Factors in The Initiation and Progression of Glomerular Injury

Research Project

Project/Area Number 06671136
Research Category

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

Allocation TypeSingle-year Grants
Research Field Kidney internal medicine
Research InstitutionNagoya University

Principal Investigator

MATSUO Seiichi  Nagoya University Faculty of Medicine Research Associate, 医学部, 助手 (70190410)

Co-Investigator(Kenkyū-buntansha) NISHIKAWA Kazuhiro  Nagoya University Faculty of Medicine Medical Staff, 医学部, 医員
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordscomplement regulatory membrane factor / glomerulonephritis / rat experimental nephritis model / monoclonal antibody / cDNA probe / tubulointerinterstitial injury / 腎灌流 / 腎臓 / 細胞膜 / 遺伝子プローブ
Research Abstract

This project was performed to elusidate the in vivo role of complement regulatory membrane factors (CRMFs) in the pathegenesis of glomerular injury. CRMFs work at two levels, i. e., the level of C3 amplification and the level of formation of membrane attack complex (MAC). The following new findings were obtained from this research project. (1) Both in human and rats, CRMFs were significantly expressed in the normal kidney including glomeruli, and in other organs. (2) Systemic suppression of the function of these factors in vivo by neutralizing monoclonal antibodies result in the endotoxin shock-like symptoms in rats. It was demonstrated for the first time by this finding that CRMFs play crucial roles for the protection of host organs from the spontaneously occurring complement attack. (3) Using an isolated kidney perfusion system developed in our laboratory, selective suppression of CRMFs in the kidney was achieved in rats. When complement-dependent glomerular injury was induced in the … More se CRMF-suppressed rats, glomerular injury was significantly enhanced with increased deposition of complement activation products. From these findings, it was testified in vivo for the first time that CRMFs in the glomeruli play protective roles in the pathogenesis of this kind of glomerular injury.
The following preliminary findings concerning the role of CRMFs in the pathogenesis of tubulointerstitial injury were also obtained by the present research project. (1) Functional suppression of tubulointerstitial CRMF resulted in the development of tubulointerstitial lesion without any complement-activating stimuli. Thus, CRMFs are important for maintaining the normal integrity of the kidney. (2) Functional suppression of CRMFs in the peritubular capillaries resulted in the increased permeability for plasma proteins, and in the tubulointerstitial injury. It is concluded that promotion of the research in this field must greatly contribute to the understanding of the mechanisms of progressive renal injury. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Funabashi,S: "Tissue distribution of complement regulatory membrane proteins in rats." Immunology. 81. 444-451 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ichida,S: "Localization of complement regulatory proteins in the normal human kidney." kidney International. 46. 89-96 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Matsuo.S: "In vivo effects of monoclonal antibodies which functionally inhibit complement regulatory proteins in rats." Journal of Experimental Medicine. 180. 1619-1627 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Matsuo,S: "The role of CD59 in the complement-mediated glomerular injury in rats." Kidney International. 46. 191-200 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ito,Y: "Pathogenic significance of interleukin-6 in a patient with anti-GBM antibody induced glomerulonephritis." American Journal of Kidney Disease. 26. 72-79 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nishikage.H: "The role of a complement regulatory protein in rat mesangial glomerulonephritis." Journal of The American Society of Nephrology. 6. 234-242 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nomura.A: "Tubulointerstitial injury induced in rats by a monoclonal antibody which inhibits function of a membrane inhibitor of complement." Journal of Clinical Investigation. 96. 2348-2356 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yuzawa.Y: "Interaction of antibody with Forssman antigen in Guinea pigs." American Journal of Pathology. 146. 1260-1272 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hatanaka,Y: "Role of a rat membrane inhibitor of complement in antibasement membrane antibody-induced renal injury." Kidney International. 48. 1728-1737 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Funabashi K,Okada N,Matsuo S,Yamamoto T,Morgan BP and Okada H.: "Tissue distribution of complement regulatory membrane proteins in rats." Immunology. 81. 444-451 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ichida S,Yuzawa Y,Okada H,Yoshioka K and Matsuo S.: "Localization of complement regulatory proteins in the normal human kidney." kidney Int. 46. 89-96 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Matsuo S,Ichida S,Takizawa H,Okada N,Baranyi L,Iguchi A,Morgan BP and Okada H: "In vivo effects of monoclonal antibodies which functionally inhibit complement regulatory proteins in rats." J Exp Med. 180. 1619-1627 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Matsuo S,Nishikage H,Nomura A,Yoshida F,Piddlesden SJ and Morgan BP: "The role of CD59 in the complement-mediated glomerular injury in rats." Kidney Int. 46. 191-200 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yuzawa Y,Brett J,, Fukatsu A,Matsuo S,Caldwell PRB,Niesen N,Milgrom F,Godman G,Stern D and Andres G: "Interaction of antibody with Forssman antigen in Guinea pigs." Am J Pathol. 146. 1260-1272 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hatanaka Y,Yuzawa Y,Nishikawa F,Fukatsu A,Okada N,Okada H,Mizuno M and Matsuo S: "Role of a rat membrane inhibitor of complement in anti-basement membrane antibody-induced renal injury." Kidney Int. 48. 1728-1737 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ito Y,Fukatsu A,Baba M,Mizuno M,Ichida S,Sado Y and Matsuo S: "Pathogenic significance of interleukin-6 in a patient with antiglomerular basement membrane antibody-induced glomerulonephritis with multinucleated giant cells." Am J Kidney Dis. 26. 72-79 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nishikage H,Baranyi L,Okada H,Okada N,Isobe K,Nomura A,Yoshida F and Matsuo S: "The role of a complement regulatory protein in rat mesangial glomerulonephritis." J Am Soc Nephrol. 6. 234-242 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nomura A,Nishikawa K,Yuzawa Y,Okada H,Okada N,Morgan BP,Piddlesden SJ,Nadai M,Hasegawa T and Matsuo S: "Tubulointerstitial injury induced in rats by a monoclonal antibody which inhibits function of a membrane inhibitor of complement." J Clin Invest. 96. 2348-2356 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nishikage H: "The role of a complement regulatory protein in rat mesangial glomerulonephritis." Journal of The Americal Society of Nephrology. 6. 234-242 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ito Y: "Pathogenic significance of interleukin-6 in a patient with anti-GBM antibody induced glomerulonephritis." American Journal of Kidney Disease. 26. 72-79 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nomura A: "Tubulointerstitial injury induced in rats by a monoclonal antibody which inhibits function of a membrane inhibitor." Journal of Clinical Investigation. 96. 2348-2356 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yuzawa Y: "Interaction of antibody with Forssman antigen in Guinea pigs." American Journal of Pathology. 146. 1260-1272 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hatanaka Y: "Role of a rat membrane inhibitor of complement in anti-GBM antibody-induced renal injury." Kidney International. 48. 1728-1737 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsuo,S.: "In vivo effects of monoclonal antibodies which functionally inhibit complement regulatory proteins in rats." journal of Experimental Medicine. 180. 1619-1627 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Matsuo,S.: "The role of CD59 in the complement-mediated glomerular injury in rats." Kidney International. 46. 191-200 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ichida,S.: "Localization of complement regulatory proteins in the normal human kidney." Kidney International. 46. 89-96 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Funabashi,K.: "Tissue distribution of complement regulatory membrane proteins in rats." Immunology. 81. 444-451 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miyazato,H.: "The target antigen of anti-tubular basement membrane antibody-mediated interstitial nephritis." Autoimmunity. 18. 259-265 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshida,F.: "Renal lesions of FGS strain of mice: A spontaneous animal model of progressive glomerulosclerosis." Nephron. 66. 317-325 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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