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Research for Precursors of Mast Cells using Mast Cell-Deficient Ws/Ws Rats.

Research Project

Project/Area Number 05670192
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionOSAKA UNIVERSITY

Principal Investigator

KASUGAI Tsutomu  Osaka University, Pathology, Associate Professor, 医学部, 講師 (80214310)

Co-Investigator(Kenkyū-buntansha) HIROTA Seiichi  Osaka University, Pathology, Assistant Professor, 医学部, 助手 (50218856)
JIPPO Tomoko  Osaka University, Pathology, Assistant Professor, 医学部, 助手 (70252658)
KITAMURA Yukihiko  Osaka University, Pathology, Professor, 医学部, 教授 (70028520)
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)
KeywordsWs / Ws rats / c-kit receptor / FcepsilonRI / histamine / stem cell factor (SCF) / Cultured mast cells / precursor of mast cell / Nippostrongylus brasiliensis / interleukin‐3(IL‐3) / マスト前駆細胞 / 高親和性IgEレセプター(FcεRI) / W / W^vマウス / CFU-Mast
Research Abstract

(1) Ws/Ws rats have a small deletion at the tyrosine kinase domain of the c-kit gene, and practically no mast cells were detectable when the tissues were stained with alcian blue. Because alcian blue stains proteoglycans, there is a possibility that immature mast cells that do not contain a sufficient amount of proteoglycans are not detectable by this method. The histamine content in the skin of Ws/Ws rats was 0.3% that of control normal (+/+) rats. Because the number of alcian blue-positive mast cells in the skin of Ws/Ws rats was also 0.3% that of +/+ rats, histamine in the skin seemed to be concenrated to alcian blue-positive mast cells. Because mast cells in the skin of +/+ rats express messenger RNA (mRNA) of FcepsilonRI beta-subunit and c-kit, we examined the expression of FcepsilonRI beta-subunit and c-kit mRNA in the skin of Ws/Ws rats. No FcepsilonRI beta-subunit-expressing and no c-kit expressing cells were detectable in the skin of Ws/Ws rats by in situ hybridization histoch … More emistry. The present result suggests the absence of immature mast cells in tissues of Ws/Ws rats.
(2) Cultured mast cells (CMC) did develop when bone marrow cells of Ws/Ws rats were cultured in the presence of concanavalin A-stimulated spleen cell conditioned medium (ConA-SCM). Although the proliferative response of CMC derived from Ws/Ws rats to Con A-SCM was comparable to that of CMC derived from +/+ rats, the proliferative response of Ws/Ws CMC to rat recombinant stem cell factor (rrSCF ; a ligand for the c-kit receptor) was much lower than that of +/+ CMC.Although CMC showed the phenotype of mucosal-type mast cells (MMC), +/+and Ws/Ws CMC acquired the phenotype of connecitive tissue-type mast cells (CTMC), when they cocultured with +/+ fibroblasts in the presence of ConA-SCM.Moreover, a fibroblast cell line derived from Sl/Sl mouse embryos that did mot produce SCF did not support the survival of both +/+ and Ws/Ws CMC but did induce the CTMC-like phenotype in about half of +/+ and Ws/Ws CMC when their survival was supported by the addition of ConA-SCM.The normal signal transduction through the c-kit receptor did not appear to be prerequisite for the acquisition of CTMC-like phenotype.
(3) Precursors of mast cells were defined as cells that formed mast-cell colonies in methylcellulose culture (CFU-mast). Mononuclear cells (MNC) were obtaineds from the bone marrow, peripheral blood, and small intestine of +/+ and Ws/Ws rats. In the culture containing ConA-SCM alone, the numbers of mast-cell colonies produced by Ws/Ws MNC were comparable with those of +/+ MNC.In the culture containing both ConA-SCM and SCF,the numbers of mast-cellcolonies produced by +/+ blood MNC were 107 times as great as that of Ws/Ws blood MNC.Using this culture condition, we investigated changes in concentration of CFU-mast in the bone marrow, blood, and intestine of +/+ rats after infection with Nippostrongylus brasiliensis (NB), which induced marked mast-cell accumulation in the small intestine. The concentration of CFU-mast in blood dropped to 21% of preinfection levels 1 week after the NB infection. In contrast, a sevenfold increase of CFU-mast occurred in the small intestine. The proportion of CFU-mast in s phase of the cell cycle remained at low levels in the bone marrow and blood after NB infection, but it increased significantly in the small intestine. The present result suggests that NB infection induces the invasion of CFU-mast into the intestine from blood and their subsequent proliferation in the tissue site. Less

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] Kasugai T: "Infection of Nippostrongylus brasiliensis induces normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit." Blood. 81. 2521-2529 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Arizono N: "Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cell in genetically mast-cell deficient Ws/Ws rats." Blood. 81. 2572-2578 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Onoue H: "Absence of immature mast cells in the skin of Ws/Ws rats with a small deletion at tyrosene kinase domain of the c-kit gene." Am J Pathol. 142. 1001-1003 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kasugai T: "Deficient differentiation of mast cells in the skin of mi/mi mice:Usefulness of in situ hybridization." Am J Pathol. 143. 1-11 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tei H: "Characterization of cultured mast cells derived from Ws/Ws mast cell-deficient rats with a small deletion at the kinase domain of c-kit." Blood. 83. 916-925 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kasugai T: "Infection of nippostrongylus brasiliensis induces invasion of mast cell precursors from peripheral blood to small intestine." Blood. (in press.).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kitamura Y: "Hematopoietic Lineages:Regulation of Cell Production and Development." Marcel Dekker,New York,NY.(in press.),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kitamura Y: "Biologecal and Molecular Aspects of Mast Cells and Bosophil Differentiation and Function." Raven press,New York,NY.(in press.),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kasugai T et al.: "Infection of Nippostrongylus brasiliensis induces normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit." Blood. 81. 2521-2529 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Arizono N et al.: "Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cell in genetically mast-cell deficient Ws/Ws rats." Blood. 81. 2572-2578 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Onoue H et al.: "Absence of immature mast cells in the skin of Ws/Ws rats with a small deletion at tyrosine kinase domain of the c-kit gene." Am J Pathol. 142. 1001-1003 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kasugai T et al.: "Deficient differentiation of mast cells in the skin of mi/mi mice : Usefulness of in situ hybridization." Am J Pathol. 143. 1-11 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tei H et al.: "Characterization of cultured mast cells derived from Ws/Ws mast cell-deficient rats with a small deletion at the kinase domain of c-kit." Blood. 83. 916-925 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kasugai T et al.: "Infection of Nippostrongylus brasiliensis induces invasion of mast cell precursors from peripheral blood to small intestine." Blood. (in Press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kitamura Y et al.: "Marcel Dekker, New York, NY.Hematopoietic Lineages : Regulation of Cell Production and Development." (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kitamura Y et al.: "Raven Press, New York, NY.Biological and Molecular Aspects of Mast Cells and Bosophil Differentiation and Function." (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kasugai T: "Infection of Nippostrongylus brasiliensis induces normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit." Blood. 81. 2521-2529 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Arizono N: "Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cell in genetically mast-cell deficient Ws/Ws rats." Blood. 81. 2572-2578 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Onoue H: "Absence of immature mast cells in the skin of Ws/Ws rats with a small deletion at tyrosine kinase domain of the c-kit gene." Am J Pathol. 142. 1001-1003 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kasugai T: "Deficient differentiation of mast cells in the skin of mi/mi mice:Usefulness of in situ hybridization." Am J Pathol. 143. 1-11 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tei H: "Characterization of cultured mast cells derived from Ws/Ws mast cell-deficient rats with small deletion at the kinase domain of c-kit." Blood. 83. 916-925 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kasugai T: "Infection of Nippostrongylus brailiensis insuces invasion of mast cell precursors from peripheral blood to small intestine." Blood. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Kitamura Y: "Hematopoietic Lineages:Regulation of Cell Production and Development." Marcel Dekker,New York,NY.(in press.),

    • Related Report
      1994 Annual Research Report
  • [Publications] Kitamura Y: "Biological and molecular Aspects of Mast Cells and Bosophil Differentiation and Function." Raven Press,New York,NY.(in press.),

    • Related Report
      1994 Annual Research Report
  • [Publications] Kasugai T: "Infection of Nippostrongylus brasiliensis induces normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit." Blood. 81. 2521-2529 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kasugai T: "Deficient differentiation of mast cells in the skin of mi/mi mice:Usefulness of in situ hybridization." Am J Pathol. 143. 1337-1347 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ogasawara J: "Lethal effect of the anti-Fas antibody in mice." Nature. 364. 806-809 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Arizono N: "Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cell in genetically mast-cell deficient Ws/Ws rats." Blood. 81. 2572-2578 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Morimoto M: "Age-dependent amelioration of hypoplastic anemia in Ws/Ws rats with a small deletion at the kinase domain of c-kit." Blood. 82. 3315-3320 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Onoue H: "Absence of immature mast cells in the skin of Ws/Ws rats with a small deletion at tyrosine kinase domain of the c-kit gene." Am J Pathol. 142. 1001-1007 (1993)

    • Related Report
      1993 Annual Research Report

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

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