1996 Fiscal Year Annual Research Report

gp130シグナルによる赤血球、顆粒球、巨核球産生法の確立とその分子機構の解明

Research Project

Project/Area Number	07407023
Research Institution	The University of Tokyo
Principal Investigator	中畑龍俊東京大学, 医科学研究所, 教授 (20110744)
Co-Investigator(Kenkyū-buntansha)	渡辺すみ子東京大学, 医科学研究所, 助手 (60240735) 辻浩一郎東京大学, 医科学研究所, 助教授 (50179991)
Keywords	gp130 / 可溶性IL-6受容体(sIL-6R) / 赤芽球分化 / 巨核球分化 / c-Kit / HML-1 / GATA-1 / EPOR
Research Abstract	(1)FACSを用いた解析により、ヒトCD34^+細胞はgp130^+IL-6R^+とgp130^+IL-6R^-細胞に分画でき、赤芽球系前駆細胞、巨核球系前駆細胞、未分化造血前駆細胞は後者に含まれることが明らかとなった(J Exp Med184:1357,1996)。 (2)CD34^+gp130^+IL-6R^-細胞は可溶性IL-6受容体(sIL-6R)とIL-6によるgp130の直接の活性化およびSCFによるc-Kitの活性化によりEPO非依存性に赤血球にまで増殖・分化できることが明らかとなった(J Exp Med183:837,1996)。 (3)巨核球系前駆細胞は全てCD34^+gp130^+IL-6R^-細胞分画に属し、この細胞はTPOとは全く独立にsIL-6R+IL-6+SCF存在下で巨核球にまで増殖・分化できることが明らかとなった(Blood in press) (4)細胞内シグナル伝達を分子生物学的手法を用いて解析するため、ダウン症に合併した急性巨核芽球性白血病患児より多分化能を持った細胞株(HML-1)を樹立した。 (5)HML-1細胞はgp130,c-Kitは発現しているがIL-6Rは発現していないことからモデル細胞として適していると考えられる。この細胞を用いて各種サイトカインに対する反応性、刺激に伴う分化マーカーの変化を検討した。 (6)HML-1細胞はsIL-6R+IL-6+SCF刺激により赤芽球系に分化できることが明らかとなり、この際変化する各種転写因子などを検討した。 (7)HML-1細胞はsIL-6R+IL-6+SCF刺激により著明にGATA-1,NFE2,EPORなどの発現がmRNAレベルで増強することが明らかとなった。今回の検討でEPOなしでもgp130の活性化により赤血球まで誘導できることを確認することができな検討が重要となってきた。

Research Products

(26 results)

All Other

All Publications (26 results)

[Publications] Tajika K.: "A novel aspect of the maturation step of megakaryocytes in thrombopoiesis:bundle formation of microtubules in megakaryocytes" Exp.Hematol.24. 291-298 (1996)
[Publications] Sawai N.: "Aberrant growth of granulocyte-macrophage progenitors in juvenile chronic myelogenous leukemia in serum-free culture" Exp.Hematol.24. 116-122 (1996)
[Publications] Kojima S.: "Measurement of endogeneous plasma granulocyte colony-stimulating factor in patients with acquired aplastic anemia by a sensitive chemiluminescent immunoassay" Blood. 87(4). 1303-1308 (1996)
[Publications] Okumura N.: "Chemotactic and chemokinetic activity of stem cell factor on murine hematopoietic progenitors" Blood. 87(10). 4100-4108 (1996)
[Publications] Tanaka R.: "Characteristics of peripheral blood progenitor cells(PBPC)mobilized by Filgrastim(rHuG-CSF)in normal healthy volunteers:dose-effect relationship for filgrastim with the character of mobilized PBPC" Brit.J.Haematol.92. 795-803 (1996)
[Publications] Sui X.: "Erythropoietin-independent erythrocyte production:signals through gp130 and c-Kit dramatically promote erythropoiesis from human CD34^+ cells" J.Exp.Med.183(3). 837-845 (1996)
[Publications] Yoshida K.: "Targeted disruption of gp130,a common signal transducer for the interleukin 6 family of cytokines,leads to myocardial and hematological disorders" Proc.Natl.Acad.Sci.USA. 93. 407-411 (1996)
[Publications] Saito H.: "Selective growth of human mast cell induced by steel factor,IL-6,and prostaglandin E_2 fromcord blood mononuclear cells" J.Immunol.157. 343-350 (1996)
[Publications] Igarashi Y.: "Characteristics of histamine release from cultured human mast cells" Clin.Exp.Allergy. 26. 597-602 (1996)
[Publications] Ishiguro A.: "Reference intervals for serum granulocyte colony-stimulating factor level in children" J.Pediatr.128(2). 208-212 (1996)
[Publications] Nakahata T.: "Role of glycoprotein 130 and c-Kit signaling in the proliferation and differentiation of human hemopoietic progenitor cells" Cancer Chemother.Pharmacol.38(Suppl). S64-S68 (1996)
[Publications] Toru H.: "Induction of the hihg-affinity IgE receptor(Fc ε RI)on human cultured mast cells by IL-4" Int.Immunol.8(9). 1367-1373 (1996)
[Publications] Tajima S.: "Analysis of interleukin 6 receptor and gp130 expressions and proliferative capability of human CD34^+ cells" J.Exp.Med.184. 1357-1364 (1996)
[Publications] Yanagida M.: "Interferon-γ promotes survival and FcεRI-mediated histamine release in cultured human mast cells" Immunology.89. 547-552 (1996)
[Publications] Nakahata T.: "Ex vivo expansion of human primitive hemopoietic progenitors" Stem Cells.(in press).
[Publications] Muraoka K.: "Defective response to thrombopoietin and impared expression of c-mpl mRAD in bone marrow cells in congenital amegakaryocytic thrombocytopenia" Brit.J.Haematol.(in press).
[Publications] Sui X.: "Soluble IL-6 receptor with IL-6 stimulates megakaryopoiesis form human CD34_+ cells through gp130 signaling" Blood. (in press).
[Publications] Toru H.: "IL-4 induces homotypic aggregation of human mast cells by promoting LFA-1/ICAM-1 adhesion molecules" Blood. (in press).
[Publications] Muraoka K.: "Thrombopoietin-independent effect of interferon-γ on the proliferation of human megakaryocyte progenitors" Brit.J.Haematol.(in press).
[Publications] Yanagida M.: "Inhibitory effect of a chymotrypsin-like inhibitor,N-Tosyl-L-phenylalanyl chloromethyl ketone on histamine release from cultured human mast cells" J.Pharm.Pharmth.(in press).
[Publications] Yoshida M.: "Thrombopoietin stimulate the proliferation of human megakaryocytic,erythroied,myeloid,and multipotentioal hemopoietic progenitors in serum-free culture" Brit.J.Haematol.(in press).
[Publications] Nishijima I.: "Hematopoietic and lymphopoietic responses in human GM-CSF receptor transgenic mice injected with human GM-CSF" Blood. (in press).
[Publications] Nakahata T.: "Bone Marrow Transplantation-Basic and Clinical Studies" Springer-Verlag Tokyo, pp47-63 (1996)
[Publications] Watanabe S.: "Bone Marrow Transplantation-Basic and Clinical Studies" Springer-Verlag Tokyo, pp123 (1996)
[Publications] Tani K.: "Bone Marrow Transplantation-Basic and Clinical Studies" Springer -Verlag Tokyo, pp201-206 (1996)
[Publications] Ikebuchi K.: "Transfusion and Hematopoietic Stem Cells-Proceedings of the 6th Hokkaido Sympoium on Transfusion Medicine" Blackwell Science Ltd., 111-117 (1996)

1996 Fiscal Year Annual Research Report

gp130シグナルによる赤血球、顆粒球、巨核球産生法の確立とその分子機構の解明

Principal Investigator

中畑 龍俊 東京大学, 医科学研究所, 教授 (20110744)

Research Products

[Publications] Tajika K.: "A novel aspect of the maturation step of megakaryocytes in thrombopoiesis:bundle formation of microtubules in megakaryocytes" Exp.Hematol.24. 291-298 (1996)

[Publications] Sawai N.: "Aberrant growth of granulocyte-macrophage progenitors in juvenile chronic myelogenous leukemia in serum-free culture" Exp.Hematol.24. 116-122 (1996)

[Publications] Kojima S.: "Measurement of endogeneous plasma granulocyte colony-stimulating factor in patients with acquired aplastic anemia by a sensitive chemiluminescent immunoassay" Blood. 87(4). 1303-1308 (1996)

[Publications] Okumura N.: "Chemotactic and chemokinetic activity of stem cell factor on murine hematopoietic progenitors" Blood. 87(10). 4100-4108 (1996)

[Publications] Tanaka R.: "Characteristics of peripheral blood progenitor cells(PBPC)mobilized by Filgrastim(rHuG-CSF)in normal healthy volunteers:dose-effect relationship for filgrastim with the character of mobilized PBPC" Brit.J.Haematol.92. 795-803 (1996)

[Publications] Sui X.: "Erythropoietin-independent erythrocyte production:signals through gp130 and c-Kit dramatically promote erythropoiesis from human CD34^+ cells" J.Exp.Med.183(3). 837-845 (1996)

[Publications] Yoshida K.: "Targeted disruption of gp130,a common signal transducer for the interleukin 6 family of cytokines,leads to myocardial and hematological disorders" Proc.Natl.Acad.Sci.USA. 93. 407-411 (1996)

[Publications] Saito H.: "Selective growth of human mast cell induced by steel factor,IL-6,and prostaglandin E_2 fromcord blood mononuclear cells" J.Immunol.157. 343-350 (1996)

[Publications] Igarashi Y.: "Characteristics of histamine release from cultured human mast cells" Clin.Exp.Allergy. 26. 597-602 (1996)

[Publications] Ishiguro A.: "Reference intervals for serum granulocyte colony-stimulating factor level in children" J.Pediatr.128(2). 208-212 (1996)

[Publications] Nakahata T.: "Role of glycoprotein 130 and c-Kit signaling in the proliferation and differentiation of human hemopoietic progenitor cells" Cancer Chemother.Pharmacol.38(Suppl). S64-S68 (1996)

[Publications] Toru H.: "Induction of the hihg-affinity IgE receptor(Fc ε RI)on human cultured mast cells by IL-4" Int.Immunol.8(9). 1367-1373 (1996)

[Publications] Tajima S.: "Analysis of interleukin 6 receptor and gp130 expressions and proliferative capability of human CD34^+ cells" J.Exp.Med.184. 1357-1364 (1996)

[Publications] Yanagida M.: "Interferon-γ promotes survival and FcεRI-mediated histamine release in cultured human mast cells" Immunology.89. 547-552 (1996)

[Publications] Nakahata T.: "Ex vivo expansion of human primitive hemopoietic progenitors" Stem Cells.(in press).

[Publications] Muraoka K.: "Defective response to thrombopoietin and impared expression of c-mpl mRAD in bone marrow cells in congenital amegakaryocytic thrombocytopenia" Brit.J.Haematol.(in press).

[Publications] Sui X.: "Soluble IL-6 receptor with IL-6 stimulates megakaryopoiesis form human CD34_+ cells through gp130 signaling" Blood. (in press).

[Publications] Toru H.: "IL-4 induces homotypic aggregation of human mast cells by promoting LFA-1/ICAM-1 adhesion molecules" Blood. (in press).

[Publications] Muraoka K.: "Thrombopoietin-independent effect of interferon-γ on the proliferation of human megakaryocyte progenitors" Brit.J.Haematol.(in press).

[Publications] Yanagida M.: "Inhibitory effect of a chymotrypsin-like inhibitor,N-Tosyl-L-phenylalanyl chloromethyl ketone on histamine release from cultured human mast cells" J.Pharm.Pharmth.(in press).

[Publications] Yoshida M.: "Thrombopoietin stimulate the proliferation of human megakaryocytic,erythroied,myeloid,and multipotentioal hemopoietic progenitors in serum-free culture" Brit.J.Haematol.(in press).

[Publications] Nishijima I.: "Hematopoietic and lymphopoietic responses in human GM-CSF receptor transgenic mice injected with human GM-CSF" Blood. (in press).

[Publications] Nakahata T.: "Bone Marrow Transplantation-Basic and Clinical Studies" Springer-Verlag Tokyo, pp47-63 (1996)

[Publications] Watanabe S.: "Bone Marrow Transplantation-Basic and Clinical Studies" Springer-Verlag Tokyo, pp123 (1996)

[Publications] Tani K.: "Bone Marrow Transplantation-Basic and Clinical Studies" Springer -Verlag Tokyo, pp201-206 (1996)

[Publications] Ikebuchi K.: "Transfusion and Hematopoietic Stem Cells-Proceedings of the 6th Hokkaido Sympoium on Transfusion Medicine" Blackwell Science Ltd., 111-117 (1996)

中畑龍俊東京大学, 医科学研究所, 教授 (20110744)