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Analysis of CD29/VLA integrin in T cell immune regulation and its clinical significance

Research Project

Project/Area Number 11307009
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionThe University of Tokyo

Principal Investigator

MORIMOTO Chikao  The Institute of Medical Science The University of Tokyo, Professor, 医科学研究所, 教授 (30119028)

Co-Investigator(Kenkyū-buntansha) KAWASAKI Hiroshi  The Institute of Medical Science The University of Tokyo, Assistant Professor, 医科学研究所, 助手 (80280957)
HOSONO Osamu  The Institute of Medical Science The University of Tokyo, Assistant Professor, 医科学研究所, 助手 (50190210)
TANAKA Hirotoshi  The Institute of Medical Science The University of Tokyo, Associate Professor, 医科学研究所, 助教授 (00171794)
WATANABE Sumiko  The Institute of Medical Science The University of Tokyo, Assistant Professor, 医科学研究所, 助手 (60240735)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥36,600,000 (Direct Cost: ¥36,600,000)
Fiscal Year 2000: ¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 1999: ¥26,300,000 (Direct Cost: ¥26,300,000)
KeywordsB cell progenitors cells / integrin α5β1 / Extracelluar signal-regulated kinase / p27(Kip1) / cyclin-dependent kinase / BM stromal cells / p27^<ldpl> / CD29 / VLA / インテグリン / Cas-L分子 / T細胞共刺激 / T細胞遊走 / チロシンリン酸化
Research Abstract

Attachment to bone marrow(BM)stromal cells is crucial for the normal growth and development of B-cell progenitors(pro-B). However, the molecular mechanisms by which contact facilitates the proliferation of pro-B cells are not completely understood. This study was performed to investigate this interaction.
Attachment to both KM102 and normal BM stromal cells significantly promoted the growth of Reh cells. Pretreatment of Reh cells with anti-integrin beta1 or alpha5 monoclonal antibody(mAb), but not alpha4 or ICAM-1 mAb, abrogated this enhancement of proliferation. Furthermore, stroma attachment resulted in shortening of the G(1)phase of cell cycle, significant increases cdk2 activity, degradation of cdk inhibitor p27-GST protein, and decrease in levels of p27(Kip1)protein. In addition, solid-phase cross-linking of alpha5 via immobilized antibody also resulted in extracellular signal-regulated(ERK)-2 kinase phosphorylation, increase in cdk2 activity, decrease in levels of p27(Kip1)protein, and enhanced proliferation that was inhibited by treatment with PD98059, a specific ERK inhibitor.
Integrin alpha5beta1-mediated stroma contact promotes the proliferation of B-cell progenitors through the activation of ERK-2, which in tum modulates cell cycle regulation machinery including induction of cdk2 activity and degradation of p27(Kip1)and contributing to acceleration of the G(1)phase of cell cycle progression.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Ohtsuki T, Tsuda H, Morimoto C: "Good or evil : CD26 and HIV infection."J Dermatol Sci. 22. 152-160 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iwata S, Ohashi Y, Kamiguchi K, Morimoto C: "Beta 1-integrin-mediated cell signaling in T lymphocytes"J Dermatol Sci. 23. 75-86 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Qing Y-W, Kitagawa M, Higashi M, Ishii G, Morimoto C, Harigaya K: "Activation of mitogen-activated protein kinas through α5β1 integrin is required for the cell cycle progression of B progenita cell line, Reh, on human marrow stromal cells"Exp.Hematol. 28. 1147-1157 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Munakata Y, Iwata S, Dobers J. Ishii T, Nori M, Tanaka H, Morimoto C: "Novel in Vitro effects of bucillamine : Inhibitory iffects on proinflammatory cytokine procuction and tranendothelial migration of T Cell"Arthr.and Rheum. 43. 1616-1623 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikushima H, Munakata Y, Ishii T, Iwata S, Terashima M, Tanaka H, Schlossman SF, Morimoto C: "Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor I receptor contributes to T cell activation"Proc.Natl.Acad.Sci.. 97. 8439-8444 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Homma T, Hosono O, Iwata S, Ando S, Sasaki K, Nishi T, Kawasaki H, Tanaka H, Moromoto C: "Recognition of cell surface GD3 by monoclonal antibody anti-6C2 in rheumatoid arthiritis synovial fluid"Arthr.& Rheum. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohtsuki T, Tsuda H, Morimoto C: "Good or evil : CD26 and HIV infection."J Dermatol Sci.. 22. 152-60 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iwata S, Ohashi Y, Kamiguchi K, Morimoto C.: "Related Articles. Beta 1-integrin-mediated cell signaling in T lymphocytes"J Dermatol Sci.. 23. 75-86 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Qing Y-W, Kitagawa M, Higashi M, Ishii G, Morimoto C, Harigaya K: "Activation of mitogen-activated protein kinas through α5β1 integrin is required for the cell cycle progression of B progenita cell line, Reh, on human marrow stromal cells"Exp.Hematol.. 28. 1147-1157 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Munakata Y, Iwata S, Dobers J, Ishii T, Nori M, Tanaka H, Morimoto C: "Novel in Vitro effects of bucillamine : Inhibitory iffects on proinflammatory cytokine production and tranendothelial migration of T Cell."Arthr.and Rheum. 43. 1616-1623 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikushima H, Munakata Y, Ishii T, Iwata S, Terashima M, Tanaka H, Schlossman SF, Morimoto C.: "Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation"Proc.Natl.Acad.Sci.. 97. 8439-8444 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Homma T, Hosono O, Iwata S, Ando S, Sasaki K, Nishi T, Kawasaki H, Tanaka H, Morimoto C.: "Recognition of cell surface GD3 by monoclonal antibody anti-6C2 in rheumatoid arthiritis synovial fluid"Arthr.& Rheum.. (In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohtsuki T,Tsuda H,Morimoto C: "Good or evil : CD26 and HIV infection."J Dermatol Sci. 22. 152-160 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iwata S,Ohashi Y,Kamiguchi K,Morimoto C: "Beta 1-integrin-mediated cell signaling in T lymphocytes"J Dermatol Sci. 23. 75-86 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Qing Y-W,Kitagawa M,Higashi M,Ishii G,Morimoto C,Harigaya K: "Activation of mitogen-activated protein kinas through α5β1 integrin is required for the cell cycle progression of B progenita cell line, Reh, on human marrow stromal cells"Exp.Hematol. 28. 1147-1157 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Munakata Y,Iwata S,Dobers J,Ishii T,Nori M,Tanaka H,Morimoto C: "Novel in Vitro effects of bucillamine : Inhibitory iffects on proinflammatory cytokine procuction and tranendothelial migration of T Cell"Arthr.and Rheum. 43. 1616-1623 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ikushima H,Munakata Y,Ishii T,Iwata S,Terashima M,Tanaka H,Schlossman SF,Morimoto C: "Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor I receptor contributes to T cell activation"Proc.Natl.Acad.Sci. 97. 8439-8444 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Homma T,Hosono O,Iwata S,Ando S,Sasaki K,Nishi T,Kawasaki H,Tanaka H,Moromoto C: "Recognition of cell surface GD3 by monoclonal antibody anti-6C2 in rheumatoid arthiritis synovial fluid"Arthr.& Rheum. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Iwata S, Yamaguchi N, Murakami Y, Ikushima H, Lee JF, Hosono O, Schlossman SF, and Morimoto C: "CD26/DPPIV differentially regulates the chemotaxis of T cells and monocytes toward RANTES"Int. Immunol. 11. 417-426 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Murakata Y, Umezawa Y, Iwata S, Dong R-P, Yoshida S, Ishii T and Morimoto C.: "Specific inhibition of Th2 type cytokine production from human peripheral T cells by terfenadine in vitro"Clin. Exp. Allergy. 29. 1281-1286 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hoshono O, Homma T, Kobayashi H, Munakata Y, Nojima Y, Iwamoto A, and Morimoto C.: "Decreased dipeptidyl peptidase IV enzyme activity of plasma soluble CD26 and its nverse correlation with HIV-1 RNA in HIV-1 infected individuals"Clin. Immunol.. 91. 283-295 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kamiguchi K, Tachibana K, Ohashi Y, Fujita H, Iwata S, and Morimoto C.: "Cas-L is required for β1 integrin-mediated costimulation in T cells"J. Immunol.. 163. 563-568 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohashi Y ,Iwata S ,Kamiguchi K, Morimoto C.: "Tyrosine Phosphorylation of Cas-L is a Cristical Element for T Cell Receptor-and β1 Integrin-induced T Lymphocyte Migration"J. Immunol.. 163. 3727-3734 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iwata S, and Morimoto C.: "CD26/Dipeptidyl peptidase IV in contaxt : The different roles of a multifunctional ectoenzyme in malignant transformation"J. Exp. Med.. 190. 301-305 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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