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STUDIES ON HUMAN CYTOKINE PECEPTORS WITH SPECIAL REFERENCES TO GM-CSF AND G-CSF

Research Project

Project/Area Number 04454572
Research Category

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

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

NIHO Yoshiyuki  KYUSHU UNIVERSITY,THE FIRST DEPARTMENT OF INTERNAL MEDICINE,FACULTY OF MEDICINE,PROFESSOR, 医学部, 教授 (60091287)

Co-Investigator(Kenkyū-buntansha) IWASAKI Hiromi  KYUSHU UNIVERSITY,THE FIRST DEPARTMENT OF INTERNAL MEDICINE,FACULTY OF MEDICINE,, 医学部, 医員
KUBOTA Akira  KYUSHU UNIVERSITY,THE FIRST DEPARTMENT OF INTERNAL MEDICINE,FACULTY OF MEDICINE,, 医学部, 医員
池松 渉  九州大学, 医学部, 医員
SHIMODA Kozuya  KYUSHU UNIVERSITY,THE FIRST DEPARTMENT OF INTERNAL MEDICINE,FACULTY OF MEDICINE,, 医学部, 医員
OKAMURA Seiichi  KYUSHU UNIVERSITY,THE FIRST DEPARTMENT OF INTERNAL MEDICINE,FACULTY OF MEDICINE,, 医学部, 講師 (20136435)
大野 裕樹  九州大学, 医学部, 医員
原田 直樹  九州大学, 医学部, 医員
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1992: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsG-CSF receptor / platelet / flowcytometry / c-kit / HEL / Jak 1 / Jak 2 / Syk / G-CSFレセプター / CD34陽性細胞 / 白血病 / GM-CSF / G-CSF / レセプター / モノクローナル抗体 / 刺激伝達 / JAK2 / 燐酸化 / RT-PCR / ノーザン法
Research Abstract

We developed flowcytometric assay system for cytokine receptors (granulocyte colony-stimulating factor receptor : G-CSFR,crythropoietin receptor (Epo-R) using fluorescent dye conjugated ligands. Monoclonal antibodies against GM-CSFR alpha chain and polyclonal antibodies against G-CSFR and GM-CSFR a chain. Various cytokine receptors including c-kit which is receptor for stem cell factor were examined among fresh human samples and leukemia cell lines.
Functional G-CSFRs were found on platelets and mRNA encoding G-CSFR was also detected in platelets and megakaryocytes.
Soluble G-CSFR was also detected with our developed antibodies and ligand binding assay.
Reversible transition of c-kit expression among human erythroleukemia cell line, HEL was firstly found. Some c-kit negative cell changed to positive cells and this implies that c-kit is not merely cell differentiation marker.
Signal transducers after G-CSFR were identified. Using antibodies and anti-sense oligomers against G-CSF dependent leukemic cell lines and the cell line which are induce differentiation with G-CSF,Jak1 and Jak2 tyrosine kinase are related to G-CSF induced cell proliferation and Syk tyrosine kinase is related to G-CSF induced cell differentiation.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Shimoda Kazuya: "G-CSF induces tyrosine phosphorylation of the Jak2 protein in the human myeloid G-CSF responsive and proliferative cells,but not in mature neutrophils." Biochemica Biophysica Research Communication. 203. 925-928 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimoda Kazuya: "Granulocyte colony-stimulating factor and platelet aggregation." Lancet. 341. 633 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimoda Kazuya: "Identification of a functional receptor for granulocyte colony-stimulating factor on platelets." Journal of Clinical Investigation. 91. 1310-1313 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kubota Akira: "The c-kit molecule and the surface immunophenotype of human acute leukemia." Lymphoma and Leukemia. 4. 421-428 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kubota Akira: "Analysis of c-kit expression of human erythroleukemia cell line,HEL: Clonal variation and relationship with erythroid and megakaryocytic phenotype." Leukemia Research. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ikematsu Wataru: "Surface phenotype and Ig heavy chain gene usage in chronic B-cell leukemia:Expression of myelomonocytic surface markers in CD5 chronic B-cell leukemia." Blood. 83. 2602-2610 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimoda K: "G-CSF induces tyrosine phosphorylation of the Jak2 protein in the human myeloid G-CSF responsive and proliferative cells, but not in mature neutrophils." Biochemica Biophysica Research Communication. 203. 925-928 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimoda K: "Granulocyte colony-stimulating factor and platelet aggregation." Lancet. 341. 633 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimoda K: "Identification of a functional receptor for granulocyte colony-stimulating factor on platelets." Journal of Clinical Investigation. 91. 1310-1313 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kubota A: "Y., The c-kit molecule and the surface immunophenotype of human acute leukemia." Lymphoma and Leukemia. 4. 421-428 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kubota A: "Analysis of c-kit expression of human erythroleukemia cell line, HEL : Clonal variation and relationship with erythroid and megakaryocytic phenotype." Leuk Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ikematsu W: "Surface phenotype and Ig heavy chain gene usage in chronic B-cell leukemia : Expression of myelomonocytic surface markers in CD5 shronic B-cell leukemia." Blood. 83. 2602-2610 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimoda Kazuya: "G-CSF induces tyrosine phosphorylation of the Jak2 protein in the human mycloid G-CSF responsive and proliferative cells,but not in mature neutrophils." Biochemica Biophysica Research Communication. 203. 925-928 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shimoda Kazuya: "High frequency granuloid colony-forming ability of G-CSF receptor-possessing CD34 antigen positive human umbilical cord blood hematopoietic progenitors." Experimental Hematology.

    • Related Report
      1994 Annual Research Report
  • [Publications] Kubota Akira: "The c-kit molecule and the surface immunophenotype of human acute leukemia." Lymphoma and Leukemia. 4. 421-428 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kubota Akira: "Analysis of c-kit expression of human erythroleukemia cell line,HEL:Clonal variation and relationship with erythroid and megakaryocytic phenotype." Leukemia Research. (印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] Ikematsu Wataru: "Surface phenotype and Ig heavy chain gene usage in chronic B-cell leukemia:Expression of myelomonocytic surface markers in CD5 chronic B-cell leukemia." Blood. (印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] Fukuda Takahiro: "Predominance of myeloid antigen in CD34 positive peripheral blood stem cells over those in bone marrow,after the administration of granulocyte colony-stimulating factor." European Journal of Haematology. 52. 201-206 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shimoda K.: "Identification of a functional recepter for granulocyte colony-stimulating factor on platelets." Journal of Clinical Investigation. 91. 1310-1313 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shimoda K.: "Granulocyte colony-stimulating factor and platelet agregation." Lancet. 341. 633- (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shimoda K.: "Human macrophage colony-stimulating factor levels in cerebrospinal fluid." Cytokine. 5. 250-254 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ikematsu W.: "Phenotypic and immunoglobulin heavy chain gene analysis of B cell chronic lymphocytic leukemia(B-CLL):Expression of myelomonocytic markers in CD5 negative B-CLL." Blood. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kubota A.: "Augmented production of interleukin 6 by co-culture of human bone marrow adherent cells and human leukemic cells." Biomedicine and Pharamacotherapy. 47. 379-384 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kubota A.: "The c-kit molecule and the surface immunophenotype of human acute leukemia." Lymphoma Leukemia. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tajiri J.: "Granulocyte colony-stimulating factor treatment of antithyroid drug-induced granulocytopenia." Archives of Internal Medicine. 153. 509-514 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takamatsu Y.: "Cytokine production by peripheral blood monocytes and T cells during haematopoietic recovery after intensive chemotherapy." British Journal of Haematology. 83. 21-27 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanaka T.: "Differentiation of rat myelomonocytic leukemia cell line(c-WRT-7)cells by rat preadipocyte cellline,REC A16 in vitro." Journal of Clinical and Experimental Oncology. 119. 335-341 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohhara N.: "Levels of serum granulocyte colony-stimulating factor in patients with cerebrovascular diseases." Life Science. 53. 939-943 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hayashi S.: "Sequential expression of lymphokine genes during phytohemagglutinin-stimulated mitogenesis of normal human peripheral mononuclear cells." Biomedicine and Pharmacotherapy. 47. 155-160 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Fukuda Y.: "Predominance of myeloid antigen in CD34 positive peripheral blood stem cells over those in bone marrow,after the administration of granuloyte colony-stimulating factor." European Journal of Haematology. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shimoda Kazuya: "Granulocytecolony-stimulating factor receptors on human leukemia:Biphenotypic leukemic cells posesses G-CSF receptors." Cancer Research. 52. 3252-3255 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kondo Seiji: "CD7-positive acute myeloid leukemia:Further evidence of cellular immaturity" Journal of Clinical and Experimental Oncology. 118. 386-388 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Omori Fusayuki: "Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions." Biotherapy. 4. 147-153 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] IKematsu Wataru: "Circulating CD34+ hematopoietic progenitors in the harvesting peripheral blood stem cells;Enhancement by recombinant human granulocyte colony-stimulating factor." Biotherapy. 5. 131-136 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shimoda Kazuya: "Identification of a functional receptor for granulocyte colony-stimulating factor on platelets." Journal of Clinical Investigation.

    • Related Report
      1992 Annual Research Report
  • [Publications] Shimoda Kazuya: "Granulocyte colony-stimulating factor and platelet agregation." Lancet.

    • Related Report
      1992 Annual Research Report
  • [Publications] Shimoda Kazuya: "Detection of the granulocyte colony-stimulating factor receptor using biotinylated granulocyte colony-stimulating factor:Presence of granulocyte colony-stimulating factor receptor on CD34-positive cells." Research in Experimental Medicine. 192. 245-255 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Otsuka Takesi: "Long-term survival of human myeloid progenito cells induced by a mouse bone marrow stromal cell line." International Journal of Cell Cloning. 10. 153-160 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tanaka Takesi: "Differentiation of rat myelomonocytic leukemia cell line(c-WRT-7)cells by rat preadipocyte cell line,REC A16 in vitro." Journal of Clinical and Experimental Oncology in press.

    • Related Report
      1992 Annual Research Report
  • [Publications] Shimoda Kazuya: "Serum G-CSF levels in umbilical cord blood of normal full-term neonates." Biomedicine and Pharmactherapy. 46. 337-341 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Harada Naoki: "Influence of a traditional Chinese herbal medicine,Ren-shen-yang-rong-tang(Japanese name:Ninjin-yoei-to) on production of interleukin-6 from peripheral blood mononuclear cells and bone marrow adherent cells." International Journal of Immunotherapy. 8. 141-145 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shimoda Kazuya: "Human macrophage colony-stimulating factor levels in cerebrospinal fluid." Cytokine.

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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