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2004 Fiscal Year Final Research Report Summary

Mechanisms of abnormal accommodation of cytoskeletal organization in the primary immunodeficiency disease

Research Project

Project/Area Number 14370239
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

MINEGISHI Masayoshi  Tohoku University, Hospital, Associate Professor, 病院, 助教授 (20211592)

Co-Investigator(Kenkyū-buntansha) OHASHI Yoshiyuki  Tohoku University, Hospital, Research Associate, 病院・助手 (60250825)
Project Period (FY) 2002 – 2004
KeywordsWiskott-Aldrich syndrome / WAS protein / beta-1 integrin / Signal transduction / Cytoskeletal organization
Research Abstract

WASP, the product of the gene mutated in Wiskott-Aldrich syndrome (WAS), is expressed only in lymphohematopoietic cells and is the first identified member of an expanding family of proteins involved in signaling and cytoskeletal reorganization. Recent reports have helped to understand b1-integrin activation as an important role in controlling the F-actin polymerization. In the present stgudy, we investgigated whether the interaction between the signaling through b1-integrin and that associated with WASP could be involved in the cytoskeletal organization and explored the possibility of gene therapy for WAS patients. The results obtained in the experiments were showed as follows : 1)a novel monoclonal antibody (mAb) against WASP by immunizing mice with the recombinant protein was produced. The mAb was highly specific to WASP and suitable for Western blot analysis and immunoprecipitation. 2)A flow cytometric assay using the mAb identified expression of intracytoplasmic WASP in lymphocytes … More from normal individuals. Double staining analysis with cell surface CD3, CD19, abd CD56, and intracytoplasmic molecules revealed WASP expression in each subpopulation. With regard to WASP expression in patients with WAS and X-linked thrombocytopenia (XLT), peripheral blood mononuclear cells (PBMCs) from nine patients and Epstein-Barr virus-transformed B-lymphoblastoid cell lines from seven patients examined did not show WASP expression by flow cytometric analysis. These results were confirmed by Western blot analysis. 3)WASP expression was first demonstrated in the subset of peripheral blood T cells and NK cells from two WAS patients by double staining analysis. 4)WASP was tyrosine phosphorylated by solid-phase fibronectin stimulation in leukemic T cell line, L-KAW. The same results was obtained by immobilized CD29 mAb stimulation experiments. Moreover, preincubation with cytochalasin B before fibronectin stimulation inhibited WASP tyrosine phosphorylation. The result indicated that the alteration of F-actin-based cytoskeleton was involved in WASP tyrosine phosphorylation via b1-integrin. These findings suggested the association of WASP in the b1-integrin-mediated signaling pathways. Less

  • Research Products

    (10 results)

All 2005 2004 2003 2002

All Journal Article (10 results)

  • [Journal Article] Evaluation of Hematological Reconstitution Potential of Autologous Peripheral Blood Progenitor Cells Cryopreserved by a Simple Controlled-Rate Freezing Method2005

    • Author(s)
      Kudo Y
    • Journal Title

      Tohoku J Exp Med 205

      Pages: 37-43

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Evaluation of hematological reconstitution potential of autologous peripheral blood progenitor cells cryopreserved by a simple controlled-rate freezing method.2005

    • Author(s)
      Kudo Y.
    • Journal Title

      Tohoku J.Exp.Med. 205

      Pages: 37-43

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Fludarabine- and cyclophosphamide-based nonmyeloablative conditioning regimen for transplantation of chronic granulomatous disease : possible correlation with prolonged pure red cell aplasia2004

    • Author(s)
      Fujiwara T
    • Journal Title

      Int J Hematol 79

      Pages: 293-297

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Fludarabine-and cyclophosphammide-based nonmyeloablative conditioning regimen for transplantation of chronic granulomatous disease : possible correlation with prolonged pure red cell aplasia.2004

    • Author(s)
      Fujiwara T.
    • Journal Title

      Int.J.Hematol. 79

      Pages: 293-297

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A simple controlled-rate freezing method without a rate-controlled programmed freezer provides optimal conditions for both large-scale and small-scale cryopreservation of umbilical cord blood cells2003

    • Author(s)
      Itoh T
    • Journal Title

      Transfusion 43

      Pages: 1303-1308

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The absolute number of peripheral blood CD34+ cells predicts a timing for apheresis and progenitor cell yield in patients with hematologic malignancies and solid tumors2003

    • Author(s)
      Kudoh Y
    • Journal Title

      Tohoku J Exp Med 199

      Pages: 111-118

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A simple controlled-rate freezing method without a rate-controlled programmed freezer provides optimal conditions for both large-scale and small-scale cryopreservation of umbilical cord blood cells.2003

    • Author(s)
      Itoh T.
    • Journal Title

      Transfusion 43

      Pages: 1303-1308

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The absolute number of peripheral blood CD34+ cells predicts a timing for apheresis and progenitor cell yield in patients with hematologic malignancies and solid tumors.2003

    • Author(s)
      Kudo Y.
    • Journal Title

      Tohoku J.Exp.Med. 199

      Pages: 111-118

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Flow cytometric determination of intracytoplasmic Wiskott-Aldrich syndrome Protein in peripheral blood lymphocyte subpopulation2002

    • Author(s)
      Kawai S
    • Journal Title

      J Immunol Methods 260

      Pages: 195-205

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Flow cytometric determination of intracytoplasmic Wiskott-Aldrich syndrome protein in peripheral blood lymphocyte subpopulations.2002

    • Author(s)
      Kawai S.
    • Journal Title

      J.Immunol.Methods 260

      Pages: 195-205

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

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Published: 2006-07-11  

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