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Structure of upregulated VLA-4 antigen expressed on PBL from SLE

Research Project

Project/Area Number 05670430
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionSaitama Medical School

Principal Investigator

TAKEUCHI Tsutomu  Saitama Medical School Associate Professor, 医学部, 助教授 (50179610)

Co-Investigator(Kenkyū-buntansha) ABE Tohru  Saitama Medical School Professor, 医学部, 教授 (60051207)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsSLE / VLA-4 / LFA-1 / Vasculitis / Fibronectin / Endothelial cells / Signal transduction / 接着分子
Research Abstract

Structure of VLA-4 antigen expressed on SLE T cells
In patients with SLE complicated with vasculitis, it has been demonstrated that expressions of not only LFA-1, but also VLA-4 were upregulated. Moreover, the additional high molecular weight band migrating at 180 kD of VLA-4 was obaerved in SLE with vasculitis, whereas 140 kD normal VLA-4 was detected in normal individual and SLE without vasculitis.
Adhesion function and signal transduction via VLA-4 in SLE with vasculitis
Peripheral T cells frpm SLE with vasculitis showed elevated adherence to fibronectin and VCAM-1. After adhesito VLA-4 ligands, ca influx was observed in these T cells, suggesting that this elicited the signal into the cell interior.
Signal transduction through functionally activated VLA-4 in SLE with vasculitis
We next examined the molecular interaction of signal transduction through VLA-4 in these fn these patients in which expression as well as function was upregulated. Given the evidences that intgrins trnasmit signals by binding to cytoskeltal proteins and forming mocal adhesion, talin, one of these cytoskeltal proteins which can binds to cytoplasmic domain of integrin beta chian were observed by Adherent Cell Analyzing System (ACAS) equipped with confocal optical system. We found that focal adhesion and the expression of talin were observed of unstimulated SLE T cells adhered onto fibronectin, whereas those of normal T cells were not. At same time, strong tyrosine-phosphorylation was noted adaround those focal adhesions, suggesting that these signal transduction pathways through intgrins were functionally activated and strongly expressed in T cells from SLE with vasculitis.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Takeuchi, T, et al: "Upregulated expression of integrin adhesive receptors in systemic lupus erythematosus patients with uasculitis" J Clin Invest. 92. 3008-3016 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi, T, et al: "Expression of cell adhesion molecules in the salivary and lacrimal glands of sgogren's syndrome" J Clin hab Invest. 7. 180-187 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi, T, et al: "Characterization of AE-b monoclonal antibody recogniging VHCSAGV sequence in CD45 PTPase domain" Tissue Antigens. 42. 441- (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi, T, et al: "Unusual variant of wegener's granulomatosis and the role of integrin adhesion receptors for pulmonary lesion" Jap J Rheum. 5. 1-9 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi, T, et al: "Enhanced expression of pp125FAKin peripheral T cells in patients with systemic lupus erythematosus" Arth Rheum. 37. 5377- (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi, T, et al: "Systemic lupus erythematosus with necrotiging vasculitis and upregulated expression of VLA-4 antigen" Clin Rheum. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi, T, et al: "Intractable vasculitis syndrome" Tanabe, T, and Yoshiki, T. Hokkaido Univ Press, 284 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 竹内勤: "免疫学update" 矢田純一編,中外医学社,東京, 316 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi T,Amano K,Sekine H,Koide J,and Abe T.: "Aberrant expression of VLA-4 antigen in systemic lupus erythematosus patients with vasculitis." Arth Rheum. 36. S71- (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi T,Sekine H,Koide J,Hosono H,Amano K,and Abe T.: "Reduced tyrosine phosphatase activity of CD45 molecule on peripheral blood T cells in patients with systemic lupus erythematosus." Arth Rheum. 36. S146- (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi T,Amano K,Sekine H,Koide J,and Abe T.: "Upregulated expression and function of integrin adhesive receptors in systemic lupus erythematosus patients with vasculitis." J Clin Invest. 92. 3008-3016 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Amano K,Sekine H,Itoh T,Hososno H,Koide J,Takeuchi T,and Abe T.: "An usual variant of Wegener's granulomatosis and the role of integrin adhesion receptor for pulmonary lesion." Jap J Rheum. 5. 217-226 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi T,Hosono O,Saito K,Koide J,Takano M,and Abe T.: "Enhanced expression of pp125FAK in peripheral blood T cells in patients with systemic lupus erythematosus." Arth Rheum. 37. S377- (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi T,Aoki K,Koide J,Sekine H,and Abe T.: "Systemic lupus erythematosus with necrotizing vasculitis and upregulated expression of VLA-4 antigen." Clin Rheum. (in press.). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Xu K,Katagiri S,Takeuchi T,and Tsubota K.: "Biopsy of labial salivary glands and lacrimal glands in the diagnosis of Sjogren's syndrome." J Rheum. (in press.). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi T,Sekine H,Saito K,Koide J,Mori S,and Abe T.: "Focal adhesion kinase pp125FAK is highly expressed in the peripheral blood lymphocytes on patients systemic lupus erythematosus complicated with vasculitis." (submitted for publication.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi T.,et al.: "Systemic lupus erythematosus with necrotizing vasculitis and upregulated expression of VLA-4 antigen." Clin.Rheum.(印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takeuchi T.,et al.: "Enhanced expression of pp125FAK in peripheral T cells in patients with systemic lupus erythematosus." Arth Rheum. 37. S377 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takeuchi T.,et al.: "Unusual variant of Wegener's granulomatosis and the role of integrin adhesion receptors for pulmonary lesion" Jap J Rheum. 5. 1-9 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takeuchi T.,et al.: "Upregulated expression of integrin adhesive receptors in systemic lupus erythematosus patients with vasculitis" J Clin Invest. 92. 3008-3016 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 竹内勤: "インテグリンを介したアウトサイド/インシグナル伝達と接着斑形成に関与する分子群" 日本臨床免疫学会会誌. 17. 515-524 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 竹内勤: "膠原病における血管病変" 医学のあゆみ. 171. 22-25 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Takeuchi,et al.: "Upregulated expression of integrin adhesive receptors in SLE patients with vasculitis." J.Clin.Invest.92. 3008-3016 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Saito,I.,Takeuchi,T.,et al.: "Expression of cell adhesion molecules in the salivary and lacrimal glands of Sjbgren's syndrome." J.Clin.Lab.Invest.7. 180-187 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohtake,K.,Takeuchi,T.,et al.: "Integrin VLA-5 negative primary plasma cell leukemia." Internal Medicine. 32. 565-568 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takeuchi,T.,et al: "Characterization of AE-6 monoclonal antibody recognizing VHCSAGV sequence in CD45 DTPase domain." Tissue Antigens. 42. 441 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 竹内 勤: "自己免疫疾患と接着分子" メビオ. 10. 93-98 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 竹内 勤: "インテグリンを介したT細胞活性化機構" 臨床免疫. 25. (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takeuchi,T.,et al: "Intractable vasculitis syndrome" Tanabe,T.and Yoshiki,T.eds,Hokkaido Univ.Press,Sapporo., 284 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 竹内 勤: "免疫学update-臨床医のために-" 矢田 純一編,中外医学社,東京, 316 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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