2000 Fiscal Year Annual Research Report

ヒト正常赤芽球系前駆細胞のサイトカイン惹起細胞内情報伝達系とその生理的意義の解明

Research Project

Project/Area Number	12670970
Research Institution	Hokkaido University
Principal Investigator	澤田賢一北海道大学, 大学院・医学研究科, 助教授 (90226069)
Keywords	Fas / SCF / EPO / アポトーシス / GPA / c-kit
Research Abstract	ヒトの造血系ではFas/Fas ligand(Fas-L)システムや、tumor necrosis factor-α(TNFα)などによるdeath domainを介したアポトーシスが造血調節に深く関与することが知られており、この機構の破綻が各種の疾患を引き起こすと考えられる。一方でstem cell factor(SCF)やerythropoietin(EPO)などの造血因子は血球の分化・増殖に働く。また、その存在がアポトーシス回避に働くことが報告されているが、これらの生存シグナルがFas/Fas-Lを介する死のシグナルとどのように拮抗するのかは不明である。我々は、ヒト正常赤芽球系前駆細胞のFas/Fas-L誘導アポトーシスがSCFによって阻害されることを見い出した。しかし、SCFはEPOと異なり、多系列の造血幹・前駆細胞に作用し、その受容体(c-kit)とともに造血細胞の分化・成熟およびその生存に関わるmulti-potential cytokineである。In vitroで増幅されたCFU-EのGPA発現率は90%以上と高純度であるが、c-kitの発現に関して不均一な集団であり、また、少数(<10%)の非赤芽球細胞も混在するため検討に供する細胞のSCFに対する反応特異性が問題となった。それゆえ、本年度は、ヒト正常GPA^+/c-kit^+細胞、GPA^+/c-kit^-細胞、非赤芽球細胞(GPA^-/c-kit^-細胞)を作成してこの問題を解決した。その結果、SCFによるGPA^+/c-kit^+細胞のFas誘導アポトーシスの解除はSrc family kinaseを介する情報伝達経路に依存していることを示唆した(Exp.Hematol 29:19,2001)。また、ヒト赤芽球系前駆細胞に発現する転写因子ZNF317の新規クローニングに成功し、その機能解析を解析中である。

Research Products

(11 results)

All Other

All Publications (11 results)

[Publications] Oda A.: "Signal transduction in primary cultured human erythroid cells."J Hematotherapy & Stem Cell Res. 9. 417-423 (2000)
[Publications] Tsutsumi, A.: "Heterogeneous behavior of anti-β2-glycoprotein I antibodies on various commercially available enzyme immunoassay plates coated with β2-glycoprotein I."J of Rheumatology. 27. 391-396 (2000)
[Publications] Ieko, M.: "Effects of β2-glycoprotein I and monoclonal anticardiolipin antibodies on extrinsic fibrinolysis"Sem Thrombos Hemostas. 26. 85-90 (2000)
[Publications] Kashii, Y.: "A member of forkhead family transcription factor FKHRL1 is one of the downstream molecule of phosphatidylinositol 3-kinase-Akt activation pathway in erythropoietin signal transduction."Blood. 96. 941-949 (2000)
[Publications] Koizumi, K.: "Large scale purification of human blood CD34+ cells from cryopreserved peripheral blood stem cells, using a nylon-fiber syringe system and immunomagnetic microspheres."Bone Marrow Transplant. 26. 787-793 (2000)
[Publications] Nishio, M.: "Effective high dose chemotherapy combined with CD34+ - selected autologous peripheral blood stem cell transplantation in a patient with cutaneous CD30-negative large T cell lymphoma."Bone Marrow Transplant. 25. 1315-1317 (2000)
[Publications] Notoya, A.: "Splenomegaly and chronic disseminated intravascular coagulation in Osler-Weber-Rendu disease."Am J Hematol. 65. 315-318 (2000)
[Publications] Nishio, M.: "Stem cell factor prevents Fas-mediated apoptosis of human erythroid precursor cells with Src-family kinase dependency."Exp Hematol. 29. 19-29 (2001)
[Publications] Endo, T.: "A possible role for lamivudine as prophylaxis against hepatitis B reactivation in carriers of hepatitis B who undergo chemotherapy and autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma."Bone Marrow Transplant. (in press).
[Publications] Yamaguchi, M.: "Serum-free coculture system for ex vivo expansion of human cord blood primitive progenitors and scid mouse-reconstituting cells using human bone marrow primary stromal cells."Exp Hematol. (in press).
[Publications] Nishio, M.: "Reversal of HIV associated motor neuron disease after highly active antiretroviral therapy (HAART) ."J Neurology. (in press).

2000 Fiscal Year Annual Research Report

ヒト正常赤芽球系前駆細胞のサイトカイン惹起細胞内情報伝達系とその生理的意義の解明

Principal Investigator

澤田 賢一 北海道大学, 大学院・医学研究科, 助教授 (90226069)

Research Products

[Publications] Oda A.: "Signal transduction in primary cultured human erythroid cells."J Hematotherapy & Stem Cell Res. 9. 417-423 (2000)

[Publications] Tsutsumi, A.: "Heterogeneous behavior of anti-β2-glycoprotein I antibodies on various commercially available enzyme immunoassay plates coated with β2-glycoprotein I."J of Rheumatology. 27. 391-396 (2000)

[Publications] Ieko, M.: "Effects of β2-glycoprotein I and monoclonal anticardiolipin antibodies on extrinsic fibrinolysis"Sem Thrombos Hemostas. 26. 85-90 (2000)

[Publications] Kashii, Y.: "A member of forkhead family transcription factor FKHRL1 is one of the downstream molecule of phosphatidylinositol 3-kinase-Akt activation pathway in erythropoietin signal transduction."Blood. 96. 941-949 (2000)

[Publications] Koizumi, K.: "Large scale purification of human blood CD34+ cells from cryopreserved peripheral blood stem cells, using a nylon-fiber syringe system and immunomagnetic microspheres."Bone Marrow Transplant. 26. 787-793 (2000)

[Publications] Nishio, M.: "Effective high dose chemotherapy combined with CD34+ - selected autologous peripheral blood stem cell transplantation in a patient with cutaneous CD30-negative large T cell lymphoma."Bone Marrow Transplant. 25. 1315-1317 (2000)

[Publications] Notoya, A.: "Splenomegaly and chronic disseminated intravascular coagulation in Osler-Weber-Rendu disease."Am J Hematol. 65. 315-318 (2000)

[Publications] Nishio, M.: "Stem cell factor prevents Fas-mediated apoptosis of human erythroid precursor cells with Src-family kinase dependency."Exp Hematol. 29. 19-29 (2001)

[Publications] Endo, T.: "A possible role for lamivudine as prophylaxis against hepatitis B reactivation in carriers of hepatitis B who undergo chemotherapy and autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma."Bone Marrow Transplant. (in press).

[Publications] Yamaguchi, M.: "Serum-free coculture system for ex vivo expansion of human cord blood primitive progenitors and scid mouse-reconstituting cells using human bone marrow primary stromal cells."Exp Hematol. (in press).

[Publications] Nishio, M.: "Reversal of HIV associated motor neuron disease after highly active antiretroviral therapy (HAART) ."J Neurology. (in press).

澤田賢一北海道大学, 大学院・医学研究科, 助教授 (90226069)