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Mechanism of Glomerular Injury Mediated by CD8^+ Lymphocytes in Anti-GBM Nephritis of WKY Rats

Research Project

Project/Area Number 06670216
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionNiigata University School of Medicine

Principal Investigator

YAMAMOTO Tadashi  Niigata University School of Medicine ; Institute of Nephrology, Department of Pathology ; Associate Professor., 医学部, 助教授 (30092737)

Co-Investigator(Kenkyū-buntansha) YAOITA Eishin  Niigata University School of Medicine ; Institute of Nephrology, Department of P, 医学部, 助手 (00157950)
KIHARA Itaru  Niigata University School of Medicine ; Institute of Nephrology, Department of P, 医学部, 教授 (80018324)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsAnti-GBM antibody / Glomerulonephritis / CD8 / Lymphocyte / Macrophage / Adhesion molecule / Cytokine / パ-フォリン
Research Abstract

We developed a new model of anti-glomerular basement membrane glomerulonephritis in WKY rats. The model was characterized with glomerular infiltration of CD8^+ lymphocytes and macrophages and crescent formation. Since the glomerulonephritis was suppressed in WKY rats which were treated with anti-CD8 antibody to deplete CD8^+ lymphocytes, it was presumed that the CD8^+ lymphocytes playd a central role in the induction of the glomerulonephritis. Namely the CD8^+ lymphocytes relate to the glomerular accumulation of macrophages, glomerular injury, and crescent formation in a direct or indirect manner. Therefore, this is a novel model in which lymphocytes regulate induction of glomerulonephritis.
In the present study, we examined an involvement of adhesion molecules, cytokines, and factors to injure glomerular structure. We found an increase of ICAM-1 expression in the glomerular endothelial cells at both protein and mRNA levels after injection with anti-glomerular basement membrane antibody. The increase of ICAM-1 expression correlated well with the accumulation of CD8^+ lymphocytes and macrophages and blocking of ICAM-1-LFA-1 interaction by administration of monoclonal antibodies against thesemolecules suppressed the glomerulonephritis induction. Through search for cytokines which might induce enhancement of ICAM-1 expression, we found that TNF-alpha expression in the glomeruli well-related with the glomerular ICAM-1 expression, suggesting a role of TNF-alpha. A participation of MCP-1 and perforin was suggested for the glomerular accumulation of macrophages and glomerular injury in this model.

Report

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

    (31 results)

All Other

All Publications (31 results)

  • [Publications] M.Hara 他: "Podocalyxin on the glomerular epithelial cells is endurable in various glomerular diseases." Nephron. 67. 123-124 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] R.C.Blantz 他: "Water and protein permeability is regulated by the glomerular epithelial slit diaphragm." J.Am.Soc.Nephrol.4. 1957-1964 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Kawasaki 他: "Therapeutic effect of combined treatment with monoclonal antibodies against intercellular adhesion molecule 1 and lymphocyte-function-associated antigen 1 in Masugi nephritis of WKY rats." Nephron. 71. 101-102 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Kihara 他: "Limitations of podocyte adaptation for glomerular injury in puromycin aminonucleoside nephrosis." Pathol.International. 45. 625-634 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Goto 他: "Expression and localization of inducible nitric oxide synthase (iNOS) in anti-Thy-1 glomerul onephritis." Am.J.Pathol.147. 1133-1141 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Yamamoto 他: "CD8+ lymphocytes play a central role in the development of anti-GBM nephritis through induction of ICAM-1 and Chemokines in WKY rats." Contrib.Nephrol.118. 118-121 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 山本 格.: "現代病理学大系 補遺3;糸球体腎炎とサイトカイン." 中山書店, 77-83 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 山本 格.: "内科学;糸球体疾患の成因と進展機序に関する最近の知見." 医学書院(印刷中),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kawasaki K,Yaoita E,Yamamoto T,Tamatani T,Miyasaka M,Kihara I: "Antibodies against intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 prevent glomerular injury in rat experimental crescentic glomerulonephritis." J Immunol. 150. 1074-1083 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hara M,Yanagihara T,Takada T,Itoh M,Adachi Y,Yoshizumi A,Kawasaki K,Yamamoto T,Kihara I: "Podocalyxin on the glomerular epithelial cells is endurable in various glomerular diseases." Nephron. 67. 123-124 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamamoto T,Feng L,Mizuno T,Hirose S,Kawasaki K,Kihara I,Wilson CB: "Expression of mRNA for atrial natriuretic peptide receptor subtypes in the kidney." Am J Physiol. 267. F318-F324 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hara M,Yamamoto T,Yanagihara T,Takada T,Kihara I: "Urinary excretion of podocalyxin indicates glomerular epithelial cell injuries in glomerulonephritis." Nephron. 67. 397-403 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamamoto T,Sasaki S,Fushimi K,Kawasaki K,Yaoita E,Oota K,Hirata Y,Marumo F,Kihara I: "Localization and expression of a collecting duct water channel, Aquaporin, in hydrated and dehydrated rats." Exp Nephrol. 3. 193-201 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yagi M,Yamamoto T,Nagano N,Kato S,Kusaka M,Kawasaki K,Yaoita E,Kihara I: "Transient expression of type I collagen in glomeruli with anti-Thy-1 antibody-induced mesangial proliferative lesions." Pathol International. 45. 409-414 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kawasaki K,Yaoita E,Yamamoto T,Kihara I: "Therapeutic effect of combined treatment with monoclonal antibodies against intercellular adhesion molecule 1 and lymphocyte-function-associated antigen 1 in Masugi nephritis of WKY rats." Nephron. 71. 101-102 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamamoto T,Sasaki S,Fushimi K,Ishibashi K,Yaoita E,Kawasaki K,Marumo F,Kihara I: "Vasopressin increases AQP-CD water channel in the apical membrane of collecting duct cells without affecting AQP3 distribution in Brattleboro rat." Am J Physiol. 268. C1546-C1551 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kihara I,Yaoita E,Kawasaki K,Yamamoto T: "Limitations of podocyte adaptation for glomerular injury in puromycin aminonucleoside nephrosis" Pathol International. 45. 625-634 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Goto S,Yamamoto T,Feng T,Yaoita E,Hirose S,Fujinaka H,Kawasaki K,Hattori R,Yui Y,Wilson CB: "Arakawa M,Kihara I.Expression and localization of inducible nitric oxide synthase (iNOS) in anti-Thy-1 glomerulonephritis" Am J Pathol. 147. 1133-1141 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamamoto T,Fujinaka H,Kawasaki K,Yaoita E,Feng L,Wilson CB,Kihara I: "CD8^+ lymphocytes play a central role in the development of anti-GBM nephritis through induction of ICAM-1 and chemokines in WKY rats. Contrib." Nephrol. 118. 118-121 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Kawasaki 他: "Therapeutic effect of combined treatment with monoclonal antibodies against intercellular adhesion molecule 1 andlymphocyte-function-assocated antigen 1 in Masugi nephritis of WKY rats." Nephron. 71. 101-102 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] I.Kihara 他: "Limitations of podocyte adaptation for glomerular injury in puromycin aminonucleoside nephrosis." Pathology International. 45. 625-634 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Goto 他: "Expession and localization of inducible nitric oxidesynthase(iNOS)in anti-Thy-1 glomerulonephritis." American Journal of Pathology. 147. 1133-1141 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Yamamoto 他: "CD8+lymphocytes play a central role in the development of anti-GBM nephritis through induction of ICAM-1 and Chemokines in WKY rats." Contribution Nephrology. 118. 118-121 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 山本 格: "現代病理学大系 補遺3;糸球体腎炎とサイトカイン." 中山書店, 77-83 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 山本 格.: "内科学;糸球体疾患の成因と進展機序に関する最近の知見." 医学書院(印刷中),

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Kawasaki: "Antibodies against intercellular adhesion molesion molecule-1 lymophocyte function-associated antigen-1 prevent glomerular injury in rat experimental crescentic glomerulonephritis." J.Immunology. 150. 1074-1083 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] R.C.Blantz: "The role of mesangial cell in the glomerular response to volume and angiotensin II." American J.Physiology. 264. F158-F165 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Hagiwara: "Immunochemical characterization and localization of endothelin ETB receptor." American J.Physiology. 264. R777-R783 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Hara: "Podocalyxin on the glomerular epithelial cells is endurable in vanous glomerular diseases." Nephron. 67. 123-124 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] R.C.Blantz: "Water and protein permeability isregulated by the glomerular epithelial slit diaphragm." J.American Society of Nephrology. 4. 1957-1964 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Yamamoto: "Expression of mRNA for atrial natriuretic peptide receptor subthpes in the kidney." American J.Physiology. 267. F318-F324 (1994)

    • Related Report
      1994 Annual Research Report

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

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