1989 Fiscal Year Annual Research Report

グラヌロポエチンに対するモノクロ-ナル抗体作製とそれを用いた顆粒球造血の研究

Research Project

Project/Area Number	61440054
Research Institution	Kyushu University
Principal Investigator	仁保喜之九州大学, 医学部, 教授 (60091287)
Co-Investigator(Kenkyū-buntansha)	工藤二郎九州大学, 医学部, 助手 (90148940) 岡村孝九州大学, 医学部, 助手 (30136436) 渋谷恒文九州大学, 医学部, 助手 (70133171) 岡村精一九州大学, 医学部, 講師 (20136435) 原田実根九州大学, 医学部, 講師 (00019621)
Keywords	グラヌロポエチン / 顆粒球造血 / G-CSF / GM-CSF / モノクロ-ナル抗体 / 酵素免疫測定法 / G-CSF受容体 / GM-CSF遺伝子発現
Research Abstract	グラヌロポエチン(別名CSF)は白血球のうち顆粒球の増殖・成熟分化を司る物質である。極微量のCSFが正常人、あるいは病的状態で、いかに顆粒球造血に作用しているかを明らかにするため、CSFに対するモノクロ-ナル抗体を作成し、CSFと顆粒球造血との関係、CSFのレセプタ-の解析などと多方面から顆粒球造血の研究を行った。まず、我々が作成したGーCSFに対するモノクロ-ナル抗体とポリクロ-ナル抗体とを用いるサンドイッチ型酵素抗体測定法(ELISA)で、50pg/mlの極微量まで測定できることを証明した。同様にGM-CSFの濃度測定もELISAを開発し、測定可能とした。これらの測定をさらに改善・発展させて各種患者血清中のGーCSFおよびGMーCSF濃度の測定を行い、多数の新知見が得られた。一例を示すと、細菌感染症、薬剤誘発無顆粒球症ではCSFが極めて高値を取るものが有ることが判明した。また、化学療法後の白血球減少期のCSF値は化学療法の種類や原疾患により上昇の程度に差があることを認めた。さらにヒト細胞からのGーCSFやGMーCSFを中心とする造血刺激因子産生状態を遺伝子操作的手法も併用して解析した。さらに、白血球増加作用薬のCSFを介する作用メカニズムを分析した。また、GM-CSFはス-パ-オキサイド産生など顆粒球の機能にも大きく作用することを証明した。異常な造血に関しては、CSFは白血病細胞を試験管内で増殖させることを証明した。さらにCSFの生体内投与実験も行った。一方、CSFは細胞に直接作用していることを証明した。そこで、CSFレセプタ-の解析を行い、正常好中球や骨髄性白血病細胞にレセプタ-の存在を証明し、その数および解離定数を得た。本年度も英文論文(投稿中のものを含め22編)を主体とした多数の報告を行った。

Research Products

(21 results)

All Other

All Publications (21 results)

[Publications] Omori,F.,et al.: "Measurement of human G-CSF by enzyme-linked immunosorbent assay using monoclonal antibody." Research in Experimental Medicine. 189. 163-171 (1989)
[Publications] Okamura,S.,et al.: "Expression of the cytokine genes in hematological malignancies." Acta Hematologica Japonica.52. 1423-1432 (1989)
[Publications] Yamaga,S.,et al.: "Effect of granulocyte-macrophage colony-stimulating factor on chemiluminescence of human neutrophils." International Journal of Cell Cloning. 7. 50-58 (1989)
[Publications] Asano,Y.,et al.: "Effect in liquid suspension culture of human native granulocyte colony-stimulating factor on proliferation and differentiation of blast cells from patients with acute non-lymphocytic leukemia." Cancer Journal. 2(8). 263-266 (1989)
[Publications] Omori,F.,et al.: "Measurement of human granulocyte-macrophage colony-stimulating factor(GM-CSF)by enzyme-linked immunosorbent assay." Biotherapy. 1. 161-167 (1989)
[Publications] Tanaka,T.,et al.: "Protective effect of recombinant murine granulocyte-macrophage colony-stimulating factor against Pseudomonas aeruginosa infection in leukocytopenic mice." Infection & Immunity. 57. 1792-1799 (1989)
[Publications] Asano,Y.,et al.: "Development of drug resistance in cultured clonogenic leukemic blast cells during clinical course of myeloblastic leukemia." Oncology. 46. 339-342 (1989)
[Publications] Taniguchi,S.,et al.: "Prostaglandin-mediated suppression of in vitro growth of erythroid progenitor cells." Kidney International. 36. 712-718 (1989)
[Publications] Matsuguchi,T.,et al.: "Molecular cloning of the cDNA coding for proline-rich protein(PRP):Identity of PRP as C4b-binding protein." Biochemical and Biophysical Research Communications.165(1). 138-144 (1989)
[Publications] Aso,T.,et al.: "A case of hybrid phenotypic chronic myelomonocytic leukemia transformed from aplastic anemia." Japanese Journal of Medicine. 28(3). 385-390 (1989)
[Publications] Tanaka,T.,et al.: "Effects of human recombinant interleukin 2 on murine myeloid colony formation(CFU-C)." International Journal of lmmunotherapy. 5(2). 57-63 (1989)
[Publications] Dohmen,K.,et al.: "Mitochondrial URF2 gene is highly expressed in human acute myelogenous leukemia." Blood.
[Publications] Okamura,S.,et al.: "Ubenimex stimulates production of colony-stimulating factor from human peripheral mononuclear cells in vitro." Acta Oncologica.
[Publications] Gondo,H.,et al.: "Acute leukemia during pregnancy:Association with immunemediated thrombocytopenia in mother and infant." Acta Haematologica.
[Publications] Hara,T.,et al.: "Human gamma delta cell receptor-positive cell-mediated inhibition of erythropoiesis in vitro in a patient with type I autoimmune polyglandular syndrome and pure red cell aplasia." Blood.
[Publications] Kondo,S.,et al.: "Direct action of human granulocyte colony-stimulating factor on mature human neutrophils:Flow-cytometric analysis." Research Communications in Chemical Pathology and Pharmacology,in press.
[Publications] Asano,Y.,et al.: "Drug sensitivity test for acute myeloblastic leukemia by an efficient leukemic blast colony assay using 5637-conditioned medium as a stimulator." Journal of Medicine.
[Publications] 牧野茂義,他.: "骨髄および末梢血幹細胞の簡便凍結保存法." 医学のあゆみ. 151(1). 65-66 (1989)
[Publications] 仁保喜之.: "急性骨髄性白血病とコロニ-刺激因子." 医学のあゆみ. 150(10). 637-640 (1989)
[Publications] 浅野嘉延,他.: "白血病と造血因子." 内科. 64(5). 819-824 (1989)
[Publications] Niho,Y,et al.: "In New Horizon of Tumor Immunotherapy Colony-stimulating factor-in vitro and in vivo effect." Excerpta Medica,Amsterdam,New York,Oxford., 501-521 (1989)

1989 Fiscal Year Annual Research Report

グラヌロポエチンに対するモノクロ-ナル抗体作製とそれを用いた顆粒球造血の研究

Principal Investigator

仁保 喜之 九州大学, 医学部, 教授 (60091287)

Research Products

[Publications] Omori,F.,et al.: "Measurement of human G-CSF by enzyme-linked immunosorbent assay using monoclonal antibody." Research in Experimental Medicine. 189. 163-171 (1989)

[Publications] Okamura,S.,et al.: "Expression of the cytokine genes in hematological malignancies." Acta Hematologica Japonica.52. 1423-1432 (1989)

[Publications] Yamaga,S.,et al.: "Effect of granulocyte-macrophage colony-stimulating factor on chemiluminescence of human neutrophils." International Journal of Cell Cloning. 7. 50-58 (1989)

[Publications] Asano,Y.,et al.: "Effect in liquid suspension culture of human native granulocyte colony-stimulating factor on proliferation and differentiation of blast cells from patients with acute non-lymphocytic leukemia." Cancer Journal. 2(8). 263-266 (1989)

[Publications] Omori,F.,et al.: "Measurement of human granulocyte-macrophage colony-stimulating factor(GM-CSF)by enzyme-linked immunosorbent assay." Biotherapy. 1. 161-167 (1989)

[Publications] Tanaka,T.,et al.: "Protective effect of recombinant murine granulocyte-macrophage colony-stimulating factor against Pseudomonas aeruginosa infection in leukocytopenic mice." Infection & Immunity. 57. 1792-1799 (1989)

[Publications] Asano,Y.,et al.: "Development of drug resistance in cultured clonogenic leukemic blast cells during clinical course of myeloblastic leukemia." Oncology. 46. 339-342 (1989)

[Publications] Taniguchi,S.,et al.: "Prostaglandin-mediated suppression of in vitro growth of erythroid progenitor cells." Kidney International. 36. 712-718 (1989)

[Publications] Matsuguchi,T.,et al.: "Molecular cloning of the cDNA coding for proline-rich protein(PRP):Identity of PRP as C4b-binding protein." Biochemical and Biophysical Research Communications.165(1). 138-144 (1989)

[Publications] Aso,T.,et al.: "A case of hybrid phenotypic chronic myelomonocytic leukemia transformed from aplastic anemia." Japanese Journal of Medicine. 28(3). 385-390 (1989)

[Publications] Tanaka,T.,et al.: "Effects of human recombinant interleukin 2 on murine myeloid colony formation(CFU-C)." International Journal of lmmunotherapy. 5(2). 57-63 (1989)

[Publications] Dohmen,K.,et al.: "Mitochondrial URF2 gene is highly expressed in human acute myelogenous leukemia." Blood.

[Publications] Okamura,S.,et al.: "Ubenimex stimulates production of colony-stimulating factor from human peripheral mononuclear cells in vitro." Acta Oncologica.

[Publications] Gondo,H.,et al.: "Acute leukemia during pregnancy:Association with immunemediated thrombocytopenia in mother and infant." Acta Haematologica.

[Publications] Hara,T.,et al.: "Human gamma delta cell receptor-positive cell-mediated inhibition of erythropoiesis in vitro in a patient with type I autoimmune polyglandular syndrome and pure red cell aplasia." Blood.

[Publications] Kondo,S.,et al.: "Direct action of human granulocyte colony-stimulating factor on mature human neutrophils:Flow-cytometric analysis." Research Communications in Chemical Pathology and Pharmacology,in press.

[Publications] Asano,Y.,et al.: "Drug sensitivity test for acute myeloblastic leukemia by an efficient leukemic blast colony assay using 5637-conditioned medium as a stimulator." Journal of Medicine.

[Publications] 牧野茂義,他.: "骨髄および末梢血幹細胞の簡便凍結保存法." 医学のあゆみ. 151(1). 65-66 (1989)

[Publications] 仁保喜之.: "急性骨髄性白血病とコロニ-刺激因子." 医学のあゆみ. 150(10). 637-640 (1989)

[Publications] 浅野嘉延,他.: "白血病と造血因子." 内科. 64(5). 819-824 (1989)

[Publications] Niho,Y,et al.: "In New Horizon of Tumor Immunotherapy Colony-stimulating factor-in vitro and in vivo effect." Excerpta Medica,Amsterdam,New York,Oxford., 501-521 (1989)

仁保喜之九州大学, 医学部, 教授 (60091287)