1989 Fiscal Year Annual Research Report

多能性造血幹細胞、白血病細胞に対するインタ-ロイキン、造血因子の作用機構の解析

Research Project

Project/Area Number	01480258
Research Institution	Shinshu University
Principal Investigator	赤羽太郎信州大学, 医学部, 教授 (60020715)
Co-Investigator(Kenkyū-buntansha)	小池健一信州大学, 医学部, 助手 (40143979) 中畑龍俊信州大学, 医学部附属病院, 講師 (20110744)
Keywords	多能性造血幹細胞 / 白血病細胞 / 小児 / in vitro培養 / 造血因子 / インタ-ロイキン / プロテインキナ-ゼC / Ca^<++>
Research Abstract	正常多能性造血幹細胞、白血病細胞に対する各種インタ-ロイキン(IL-1〜IL-7)、造血因子(G-CSF、GM-CSF、EP、LTF)の作用機構に関する基礎的検討を行った。本年度の主要成績として以下のごとき結果がえられた。 1)多能性造血幹細胞をin vitroで増殖させる最も効果的なインタ-ロイキン、造血因子の組み合せを検討し、マウスではIL-3とIL-6の両者の存在下で骨髄細胞を液体培養することにより、CFU-Sを大巾に増幅することが可能となった。ヒトにおいても同様の検討を行い、現在のところIL-3+IL-6が最も効果的な組み合せのように思われる。 2)小児白血病初診時、再発時の骨髄細胞を用いて、各種インタ-ロイキン、造血因子に対する反応性を検討すると、IL-3やGM-CSFで白血病細胞が著明に増殖する症例がみられた。 3)プロテインキナ-ゼ(PKC)の活性化およびdown regulationと細胞増殖の関係が明らかにされた。 4)正常多能性造血幹細胞を用いて、インタ-ロイキン、造血因子の細胞内シグナル伝達を検索するための予備実験として、成熟好中球を用いて、G-CSF、GM-CSFと反応後の細胞内Ca^<++>濃度を細胞内カルシウム顕微測定システムを用いて測定したが、充分に評価しうる結果がえられた。 5)現在まで不明であった血小板増多因子の1つがIL-6であることがin vitro、in vivoの研究で明らかになった。 6)各種小児血液疾患に対する有効な造血因子、インタ-ロイキンの臨症応用に関する有易な結果がえられた。

Research Products
(21 results)

All Other

All Publications (21 results)

[Publications] Toshimi Kobayashi: "Stochastic model for mast cell proliferation in culture of murine peritoneal cells." J.Cell.Physiol.138. 24-28 (1989)
[Publications] Akira Okano: "Effects of interleukin-6 on hematopoiesis in bone marrow-transplanted mice." Transplantation. 47. 738-740 (1989)
[Publications] Kohichiro Tsuji: "Stochastic model.for multipotential hemopoietic progenitor differentiation." J.Cell.Physiol.139. 647-653 (1989)
[Publications] Mineo Takagi: "Stimulation of connective tissue-type mast cell proliferation by crosslinking of cell-bound IgE." J.Exp.Med.170. 233-244 (1989)
[Publications] Kazuyuki Yoshizaki: "Pathogenic significance of interleukin-6(IL-6/BSF-2)in Castleman's disease." Blood. 74. 1360-1367 (1989)
[Publications] Akira Okano: "In vitro expansion of the murine pluripotent hemopoietic stem cell population in response to interleukin 3 and interleukin 6." Transplantation. 48. 495-498 (1989)
[Publications] Kohichiro Tsuji: "Synergistic action of phorbol ester and IL-3 in the induction of“connective tissue-type"mast cell proliferation." J.Immunol.144. 678-684 (1990)
[Publications] Kohichiro Tsuji: "Effects of interleukin-3 and interleukin-4 on the development of“connective tissue-type"mast cells:Interleukin-3 supports their survial and interleukin-4 triggers and supports their proliferation synergistically with interleukin-3." Blood. 75. 421-427 (1990)
[Publications] Kenichi Koike: "IL-6 enhances murine megakaryocytopoiesis in serm-free culture." Blood.
[Publications] Shigetaka Asano: "In vivo effects of recombinant human interleukin 6 in primates:Stimulated production of platelets." Blood.
[Publications] Yoichi Takaue: "Effects of recombinant human G-CSF,GM-CSF,IL-3 and interleukin-1 on the growth of highly purified human peripheral blood progenitors." Blood.
[Publications] Kazunaga Agematsu: "Successful bone marrow transplantation in a case with severe pretransplant pneumonia." Transplantation.
[Publications] Akihiko Yabuhara: "Giant lymph node hyperplasia(Castleman's disease)with spontaneous production of high leves of B-cell differentiation factor activity." Cancer. 63. 260-265 (1989)
[Publications] Yohji Hara: "Temperature-dependent formation of vacuolar and canalicular systems in association with degranulation in stimulated neutrophils." Eur.J.Haematol.42. 474-480 (1989)
[Publications] Munehiro Yamazaki: "Dopamine inhibition of superoxide anion production by polymorphonuclear leukocytes." J.Allergy Clin.Immunol.83. 967-972 (1989)
[Publications] 中畑龍俊: "造血幹細胞の増殖、分化と造血因子" 信州医学雑誌. 37. 149-164 (1989)
[Publications] 辻浩一郎: "蛋白多糖体(PSK)とヒト造血幹細胞に及ぼす影響" 日血会誌. 52. 594-600 (1989)
[Publications] 石黒精: "好中球減少に対して好中球系コロニ-刺激因子(G-CSF)が有効であった糖原病16の1例" 代謝. 26. 63-68 (1989)
[Publications] 中畑龍俊: "造血因子としてのIL4、IL5" 生体防御. 6. 207-218 (1989)
[Publications] 中畑龍俊: "造血幹細胞とIL3、IL-6" 臨床科学. 26. 206-213 (1989)
[Publications] 中畑龍俊: "Annual Review血液" 中外医学社, 12 (1989)

1989 Fiscal Year Annual Research Report

多能性造血幹細胞、白血病細胞に対するインタ-ロイキン、造血因子の作用機構の解析

Principal Investigator

赤羽 太郎 信州大学, 医学部, 教授 (60020715)

Research Products

[Publications] Toshimi Kobayashi: "Stochastic model for mast cell proliferation in culture of murine peritoneal cells." J.Cell.Physiol.138. 24-28 (1989)

[Publications] Akira Okano: "Effects of interleukin-6 on hematopoiesis in bone marrow-transplanted mice." Transplantation. 47. 738-740 (1989)

[Publications] Kohichiro Tsuji: "Stochastic model.for multipotential hemopoietic progenitor differentiation." J.Cell.Physiol.139. 647-653 (1989)

[Publications] Mineo Takagi: "Stimulation of connective tissue-type mast cell proliferation by crosslinking of cell-bound IgE." J.Exp.Med.170. 233-244 (1989)

[Publications] Kazuyuki Yoshizaki: "Pathogenic significance of interleukin-6(IL-6/BSF-2)in Castleman's disease." Blood. 74. 1360-1367 (1989)

[Publications] Akira Okano: "In vitro expansion of the murine pluripotent hemopoietic stem cell population in response to interleukin 3 and interleukin 6." Transplantation. 48. 495-498 (1989)

[Publications] Kohichiro Tsuji: "Synergistic action of phorbol ester and IL-3 in the induction of“connective tissue-type"mast cell proliferation." J.Immunol.144. 678-684 (1990)

[Publications] Kohichiro Tsuji: "Effects of interleukin-3 and interleukin-4 on the development of“connective tissue-type"mast cells:Interleukin-3 supports their survial and interleukin-4 triggers and supports their proliferation synergistically with interleukin-3." Blood. 75. 421-427 (1990)

[Publications] Kenichi Koike: "IL-6 enhances murine megakaryocytopoiesis in serm-free culture." Blood.

[Publications] Shigetaka Asano: "In vivo effects of recombinant human interleukin 6 in primates:Stimulated production of platelets." Blood.

[Publications] Yoichi Takaue: "Effects of recombinant human G-CSF,GM-CSF,IL-3 and interleukin-1 on the growth of highly purified human peripheral blood progenitors." Blood.

[Publications] Kazunaga Agematsu: "Successful bone marrow transplantation in a case with severe pretransplant pneumonia." Transplantation.

[Publications] Akihiko Yabuhara: "Giant lymph node hyperplasia(Castleman's disease)with spontaneous production of high leves of B-cell differentiation factor activity." Cancer. 63. 260-265 (1989)

[Publications] Yohji Hara: "Temperature-dependent formation of vacuolar and canalicular systems in association with degranulation in stimulated neutrophils." Eur.J.Haematol.42. 474-480 (1989)

[Publications] Munehiro Yamazaki: "Dopamine inhibition of superoxide anion production by polymorphonuclear leukocytes." J.Allergy Clin.Immunol.83. 967-972 (1989)

[Publications] 中畑龍俊: "造血幹細胞の増殖、分化と造血因子" 信州医学雑誌. 37. 149-164 (1989)

[Publications] 辻浩一郎: "蛋白多糖体(PSK)とヒト造血幹細胞に及ぼす影響" 日血会誌. 52. 594-600 (1989)

[Publications] 石黒精: "好中球減少に対して好中球系コロニ-刺激因子(G-CSF)が有効であった糖原病16の1例" 代謝. 26. 63-68 (1989)

[Publications] 中畑龍俊: "造血因子としてのIL4、IL5" 生体防御. 6. 207-218 (1989)

[Publications] 中畑龍俊: "造血幹細胞とIL3、IL-6" 臨床科学. 26. 206-213 (1989)

[Publications] 中畑龍俊: "Annual Review血液" 中外医学社, 12 (1989)

赤羽太郎信州大学, 医学部, 教授 (60020715)