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Fibroblast-dependent Proliferation of Mast Cells

Research Project

Project/Area Number 02404030
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionOsaka University

Principal Investigator

KITAMURA Yukihiko  Osaka Univ Med Sch Professor, 医学部, 教授 (70028520)

Co-Investigator(Kenkyū-buntansha) ONOUE Hitoshi  Osaka Univ Med Sch Instructor, 医学部, 助手 (70221166)
TSUJIMURA Tohru  Osaka Univ Med Sch Instructor, 医学部, 助手 (20227408)
KASUGAI Tsutomu  Osaka Univ Med Sch Instructor, 医学部, 助手 (80214310)
HIROTA Seiichi  Osaka Univ Med Sch Instructor, 医学部, 助手 (50218856)
NOMURA Shintaro  Osaka Univ Med Sch Assoc Prof, 医学部, 助教授 (80159087)
Project Period (FY) 1990 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥32,200,000 (Direct Cost: ¥32,200,000)
Fiscal Year 1993: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1992: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1991: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1990: ¥12,900,000 (Direct Cost: ¥12,900,000)
KeywordsMast Cell / Stem Cell Factor / W locus of mice / Ws locus of rats / Receptor Tyrosine Kinase / Mast Cell-Deficeint Animals / Mast Cell-Deficient Mouse / Mast Cell-Deficient Rat / stem cell factor / レセプタータイロシンキナーゼ / マスト細胞腫 / 好塩基球 / レセプター・タイロンシンカイネース / マスト細胞欠接ラット / cーkitレセプタ- / cーkitレセプタ-のリガンド / 接着因子 / マスト細胞増殖因子 / CーKit遺伝子 / Sl遺伝子座 / 線維芽細胞
Research Abstract

Fibroblast-dependent proliferation of mast cells is mediated by stem cell factor (SCF) produced by fibroblasts and c-kit receptor (KIT) expressed on the surface of mast cells. Ws studied the SCF-KIT system from various viewpoints and obtained the following results. 1). Although many KIT mutants have been found in mice, KIT mutants were not known in rats. We described the first KIT mutants in rats. We characterized the Ws (White spotting) locus of rats which encoded the KIT.2). We compared the molecular nature of murine KIT mutants with the number of mast cells in thier skin. 3). We studied the unique KIT mutation designated as Wsh. Although the Wsh mutant allele is located at the W locus, we could not find any abnormalities in the coding region of KIT gene. Since KIT was not transcribed in cultured mast cells derived from the bone marrow of Wsh/Wsh mice, the Wsh mutation was considered to be a mutation at the regulatory region. Since KIT was transcribed in erythroblasts and germ cells of Wsh/Wsh mice, the abnormality of KIT transcription appeared to be cell type specific. Moreover, we found the KIT transcription was influenced by the age in mast cells of Wsh/Wsh mice. Although an appreciable number of mast cells was found in the skin of Wsh/Wsh embryos, mast cells decreased rapidly after birth due to the abolishment of KIT transcription. 4). The mi locus of mice encodes a transcription factor of basic helix-loop-helix leucine zipper family. We demonstrated that the phenotypic abnormalities observed in mast cells of mi/mi mice was attributable to the deficeint transcription of various proteins.

Report

(5 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Tsujimura,Tohru: "Characterization of WS mutant allele of rats : a 12 base delation in tyrosine kinase domain of c-kit gene." Blood. 78. 1942-1946 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tono,Toshiharu: "c-kit gene was not transcribed in cultured mast cells of mast cell-deficient Wsh/Wsh mice that have normal number of erythrocytes and normal c-kit coding region." Blood. 80. 1448-1453 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Onoue,Hitoshi: "Absence of mast cells in the skin of Ws/Ws rats with a small deletion at tyrosine kinase domain of the c-kit gene." American Journal of Pathology. 142. 1001-1007 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kasugai,Tsutomu: "Infection of Nippostrogylus brasiliensis induced 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
      1993 Final Research Report Summary
  • [Publications] Tsujimura,Tohru: "Mast cell number in the skin of heterozygotes reflects molecular nature of c-kit mutation." Blood. 81. 2530-2538 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kasugai,Tsutomu: "Deficient differentiation of mast cells in the skin of mi/mi mice : usefulness of in situ hybridization for evaluation of mast cell phenotype." American Journal of Pathology. 143. 1337-1347 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitamura,Yukihiko: "Immunopharmacology of Mast Cells and Bsophils" Academic Press, 232 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitamura,Yukihiko: "Biological and Molecular Aspects of Mast Cell and Basophil Differentiation and Function" Raven Press (in press),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsujimura, Tohru: "Characterization of Ws mutant allele of rats : a 12 base deletion in tyrosine kinase domain of c-kit gene." Blood. 78. 1942-1946 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tono, Toshiharu: "c-kit gene was not transcribed in cultured mast cells of mast cell-deficient Wsh/Wsh mice that have normal number of erythrocytes and normal c-kit coding region." Blood. 80. 1448-1453 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Onoue, Hitoshi: "Absence of mast cells in the skin of Ws/Ws rats with a small deletion at tyrosine kinase domain of c-kit gene." American Journal of Pathology. 142. 1001-1007 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kasugai, Tsutomu: "Infection of Nippostrongylus brasiliensis induced 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
      1993 Final Research Report Summary
  • [Publications] Tsujimura, Tohru: "Mast cell number in the skin of heterozygotes reflects molecular nature of c-kit mutation." Blood. 81. 2530-2538 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kasugai, Tsutomu: "Deficient differentiation of mast cells in the skin of mi/mi mice : usefulness of in situ hybridization for evaluation of mast cell phenotype." American Journal of Pathology. 143. 1337-1347 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitamura, Yukihiko: Immunopharmacology of Mast Cells and Basophils. Academic Press, (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitamura, Yukihiko: Biological and Molecular Aspects of Mast Cell and Basophil Differentiation and Function. Raven Press, (in press),

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Onoue,Hitoshi: "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" American Journal of Pathology. 142. 1001-1007 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kasugai,Tsutomu: "Infection of N.brasiliensis induced normal increase of basophils in mast cell-deficient Ws/Ws rats" Blood. 81. 2521-2529 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tsujimura,Tohru: "Mast cell number in the skin of heterozygotes reflects molecular nature of c-kit mutation" Blood. 81. 2530-2538 (1993)

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

    • Related Report
      1993 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Development of mast cells and basophils:processes and regulation mechanisms" American Journal of Medical Sciences. 306. 185-191 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hirata,Tatsumi: "Stem cell factor induces outgrowth of c-kit-positive neurites and supports the survival of c-kit-positive neurons in DRG" Development. 119. 49-56 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Immunopharmacology of Mast Cells and Basophils" Academic Press, 232 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Gann Monograph on Cancer Research,Growth Factors in Cell Growth,Morphogenesis and Transformation" Japan Scientific Societies Press,Tokyo(in press),

    • Related Report
      1993 Annual Research Report
  • [Publications] Adachi,Shiro: "Necessity of extracellular domain-of W(c-kit)receptors for attachment of murine mast cells to fibroblasts." Blood. 79. 650-656 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tono Toshifaru: "c-kit gene was not transcribed in cultured mast cells of mast cell-deficient Wsh/Wsh mice that have normal number of erythrocytes and normal c-kit coding region." Blood. 80. 1448-1453 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Jippo-Kanemoto,Tomoko: "BALB/3T3 fibroblast conditioned meium attracts cultured mast cells derived from W/W but not from mi/mi mutant mice,both of which are deficient in mast cells." Blood. 80. 1933-1936 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Onoue,Hitoshi: "Absince of immatute mast cells in the skin of Ws/Ws rats with a small small deletion at tyrosine kinase domain of the c-kit gene." American Journal of Pathology.

    • Related Report
      1992 Annual Research Report
  • [Publications] Tsujimura,Tohru: "Mast cell number in the skin of heterozygotes reflects molecular nature of c-kit mutation." Blood.

    • Related Report
      1992 Annual Research Report
  • [Publications] Kasugai,Tsutomu: "Infection of Nippostrongylus brasiliensis induced normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit." Blood.

    • Related Report
      1992 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Progress in Allergy and Clinial Immunology" Hogrete & Huber Publishers,Tronto,

    • Related Report
      1992 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Immunopharmacology of Mast Cells and Basophils" Academic,Press,London,

    • Related Report
      1992 Annual Research Report
  • [Publications] Jozaki,Kiyoshi: "Bone marrowーderived cultured mast cells as targets of a growth activity secreted by BALB/3t3 fibroblasts." Experimental Hematology. 19. 185-190 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kanemoto,Tomoko: "Effects of culture matrix on differentiation of murine mast cells." Experimental Hematology. 19. 288-293 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Matsuda,Hiroshi: "Nerve growth factor increases development of connective tissueーtype mast cells in vitro from murine bone marrow cells." Journal of Experimental Medicine. 174. 7-14 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Niwa,Yoshiki: "Anemia and mast cell depletion in mutant rats that are homozygous at “White spotting(WS)" locus." Blood. 78. 1936-1941 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tsujimura,Tohru: "Characterization of Ws mutant allele of rats:a 12 base deletion in tyrosine kinase domain of cーkit gene." Blood. 78. 1942-1946 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Adachi,Shiro: "Necessity of extracellular domain of W(cーkit) receptors for attachment of murine cultured mast cells to fibroblasts." Blood. 79. 650-656 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Immunopharacology of Mast cells and Basophils" Academic Press,London,

    • Related Report
      1991 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Proceedings of the 14th International Congress of Allergy and Clinical Immunology" Hogrete & Huber Publishers,

    • Related Report
      1991 Annual Research Report
  • [Publications] Kitamura,Y.: "Differentiation of mast cells:processes and regulation mechanisms." Acta Haematologica Japonica. 53. 1447-1450 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Matsuda,H.: "Necessity of IgE antibodies and mast cells for manifestation of resistance against larval Haemaphysalis longicornis ticks in mice." Journal of Immunology. 144. 259-262 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ebi,Y.: "Mechanism of mast cell deficiency in mutant mice of <mi/mi>___ー genotype:an analysis by coーculture of mast cells and fibroblasts." Blood. 75. 1247-1251 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Toyota,N.: "Administration of 8ーmethoxypsoralen and ultraviolet A irradiation (PUVA) induces turnover of mast cells in the skin of C57BL/6 mice." Journal of Investigative Dermatology. 95. 353-358 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Jozaki,K.: "Proliferative potential of murine peritoneal mast cells after degranulation induced by compound 48/80,Substance P,tetraーdecanoylphorbol acetate,or calcium ionophore A23187." Journal of Immunology. 145. 4252-4259 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Jozaki,K.: "Bone marrowーderived cultured mast cells and peritoneal mast cells as target of a growth activity secreted by BALB/3T3 fibroblasts." Experimental Hematology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Kitamura,Y.: "Ontogeny of mast cells.In The Immunology of Fetus" CRC Press (Boca Raton), 320 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kitamura,Y.: "Differentiation of mast cells and phenotypic change between subpopulations.In Progress in Immunology VII" SpringerーVerlag (Berlin), 1318 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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