2003 Fiscal Year Annual Research Report

樹状細胞による造血制御に関する研究

Research Project

Project/Area Number	14570959
Research Institution	AKITA UNIVERSITY
Principal Investigator	澤田賢一秋田大学, 医学部, 教授 (90226069)
Keywords	CD34 / TNF-α / 赤芽球系前駆細胞 / 樹状細胞 / CD11c / phagocytosis / 自己免疫 / 免疫寛容
Research Abstract	純化ヒトCD34+細胞はIL-3+SCF+EPO存在下で赤芽球へ系特異的に分化・増殖する.この系にTNF-αが存在すると,赤芽球系細胞の発生が抑制され,非赤芽球系細胞の発生が促進する(Exp Hematol 30:1238,2002).従来,これらの非赤芽球系細胞は,顆粒球・マクロファージ系前駆細胞(CFU-GM)由来であると考えられてきた.しかしその形態は樹状細胞(DC)に類似し,自己赤芽球系前駆細胞と接着していた.平成15年度は,TNF-αによってCD34+細胞から誘導される非赤芽球系細胞の性状と機能を,同時に発生する自己赤芽球系前駆細胞との関連のもとに解析した.Glycophorin A陽性細胞を赤芽球系細胞(GPA+細胞),非赤芽球系細胞をGPA-細胞とした.TNF-αによるGPA-細胞の増加は,CD34+細胞の培養開始後3日目から生ずる極めて早期の現象であった.GPA-細胞の形態はDCに類似し,その一部は変性した自己赤芽球様細胞と接着していた.GPA-細胞はHLA class I、HLA class II、CD1a、CD4、CD11c、CD14、CD40とともに共刺激分子CD80、CD83、CD86を発現するDCであった.発生様式の観察で,CD34+細胞はTNF-α存在下で凝集塊を形成しつつ増殖していた.凝集塊はDCから構成されておりGPA+細胞と接して存在していた.DCのうちCD11c+細胞はapoptosisを起こしている自己GPA+細胞を選択的に接着・貪食していた.CD34+細胞を樹状前駆細胞(CD34+CD123+CD45RA+)と非樹状前駆細胞(CD34+CD123+CD45RA-)に分画し,各分画に対するTNF-αの影響を検討した.TNF-αは非DC分画におけるGPA+細胞の発生を抑制した.TNF-αはヒトCD34+細胞からのGPA+細胞の発生を直接抑制するとともにDCを同時に発生させた.DC分画中CD11c+DCは,自己GPA+細胞の接着と貪食を行なうことを明らかにした(Exp Hematol, in press).TNF-αは炎症急性期に最も早期に発現するサイトカインである.従って骨髄は造血刺激と炎症の共存によって,自己造血前駆細胞に対する自然免疫誘導の場になりうるとともに,以降の免疫応答に関与していると推定される.

Research Products

(34 results)

All Other

All Publications (34 results)

[Publications] Yamaguchi M.: "Ex vivo expansion of human UC blood primitive hematopoietic progenitors and transplantable stem cells using human primary BM stromal cells and human AB serum"Cytotherapy. 14. 109-118 (2002)
[Publications] Koizumi K.: "Hemophagocytic syndrome (HPS) in prostatic cancer revealed by disseminated carcinomatosis of the done marrow"J Urology. 168. 1101-1102 (2002)
[Publications] Osawa M.: "Erythroid expansion mediated by Gfi-1B finger protein : role in normal hematopoiesis"Blood. 100. 2769-2777 (2002)
[Publications] Goto H.: "Renal Alpha-Actinin-4 : Purification and puromycin aminonucleoside-binding property"Nephron Exp Nephrol. 93. e27-e35 (2003)
[Publications] Xiao W.: "Tumor necrosis factor-α inhibits generation of glycophorin A+cells by CD34+ cells"Exp Hematol. 30. 1238-1247 (2002)
[Publications] Itoh H.: "Mammalian HSP60 is quickly sorted into the mitochondria under conditions of dehydration"Eur J Biochem. 269. 5931-5938 (2002)
[Publications] Hirokawa M.: "Dsitinct TCRAV and TCRBV repertorie and CDR3 sequence of T lymphocytes clonally expanded in blood and GVHD lesions after human allogeneic bone marrow transplantation"Bone Marrow Transplant. 30. 915-923 (2002)
[Publications] Matsumori M.: "Characterization of the 105-kDa molecular chaperone identification, biochemical properties, and localization"Eur J Biochem. 269. 5632-5641 (2002)
[Publications] Kawabata Y.: "Clinical applications of CD34+ cell-selected peripheral blood stem cells"Therapeutic Apheresis and Dialysis. 7. 298-304 (2003)
[Publications] Koizumi K.: "Severe aplastic anemia associated with thymic carcinoma and partial recovery of hematopoiesis after thymectomy"Ann Hematol. 82. 367-370 (2003)
[Publications] Kawakubo K.: "Granular lymphocyte proliferative disorder after autologous peripheral blood stem cell transplantation for multiple myeloma"Eur J Haematol. 71. 124-127 (2003)
[Publications] Komatsuda A.: "Amyloid A-type renal amyloidosis in a patient with sarcoidosis : report of case and review of the literature"Clinical Nephrology. 60. 284-288 (2003)
[Publications] Fujishima M.: "Amyloid arthropathy resembling seronegative rheumatoid arthritis in a patient with IgD-kappa multiple myeloma"Internal Medicine. 42. 121-124 (2003)
[Publications] Komatsuda A.: "Analysis of mutations in Alpha-Actinin4 and podocin genes of patients with chronic renal failure due to sporadic focal segmental glomerulosclerosis"Renal failure. 25. 87-93 (2003)
[Publications] Lee J.: "Migration and differentiation of nuclear fluorescence-labeled bone marrow stromal cells (BMSCs) after transplantation into cerebral infarct and spinal cord injury in mice"Neuropathology. 23. 169-180 (2003)
[Publications] Saitoh H.: "The presence and longevity of peripherally expanded donor-derived TCR αβ+ mature T lymphocyte clones after allogeneic bone marrow transplantation for adult myeloid leukemias"Leukemia. 17. 1626-1635 (2003)
[Publications] Nimura T.: "Cytogenetic study of 48 patients with multiple myeloma and related disorders"Hematopathol. 43(2). 53-60 (2003)
[Publications] Wakamoto S.: "Biologic activity of RANTES in apheresis PLT Concentrates and its involvement in nonhemolytic transfusion reactions"Transfusion. 43. 1038-1046 (2003)
[Publications] Hirokawa M.: "T-cell repertoire regeneration after human allogeneic hematopoietic stem cell transplantation : Current concept and future direction"Recent Res Devel Immunology. 5. 151-157 (2003)
[Publications] Maki N.: "A nonsense mutation (R220X) in the α-galactosidese A gene causes typical Fabry disease in both genders"Clinical Nephrol. (in press).
[Publications] Ichikawa Y.: "Monitoring the expression profiles of doxorubicin-resistant leukemia cells by serial analysis of gene expression"Int J Hematol. (in press).
[Publications] Miyazaki T.: "73-kDa Molecular chaperone HS73 is a direct target of antibiotic gentamaicin"J Biol Chem. (in press).
[Publications] Fukaya H.: "Co-development of dendritic cells along with erythroid differentiation from human CD34+ cells by tumor necrosis factor-α"Exp Hematol. (in press).
[Publications] Maki N.: "Four novel mutation in the Thiazide-Sensitive Na-Cl cotransporter in Japanese patients with gitelman's sybdrome"Nephrol Dial Transplant. (in press).
[Publications] 澤田賢一, 坊垣暁之, 天崎吉晴, 小池隆夫: "E.自己免疫疾患に対する造血幹細胞移植療法:造血幹細胞基礎から遺伝し治療・再生医療へ"小澤敏也編集著,中央医学社. 7 (2002)
[Publications] 小泉和樹, 澤田賢一: "内科領域の輸血,輸血ハンドブック"台2版霜山龍志編集,医学書院. 19 (2002)
[Publications] 高橋直人, 澤田賢一: "自家末梢血幹細胞移植よるリンパ腫治療,「癌の臨床」"篠原出版社. 7 (2002)
[Publications] 澤田賢一: "MDSにおける血球分化と増殖の異常"医薬ジャーナル社,血液フロンティア. 9 (2002)
[Publications] 澤田賢一: "知って安心秋田の病気あれこれ"秋田魁新報社. 2 (2003)
[Publications] 澤田賢一: "二次性貧血,改訂第3版「外来診療のすべて」"メジカルビュー社. 2 (2003)
[Publications] 小松田敦, 澤田賢一: "「末梢血幹細胞移植療法」,リウマチ性疾患治療の最前線,内科"南江堂. 4 (2004)
[Publications] 澤田賢一: "幹細胞・造血因子"森真由美編集,医薬ジャーナル社(印刷中).
[Publications] 澤田賢一: "鉄欠乏性貧血,「血液の事典」"朝倉書店(印刷中).
[Publications] 澤田賢一: "改訂第4版「疾患別最新処方」悪性貧血"メジカルビュー社(印刷中).

2003 Fiscal Year Annual Research Report

樹状細胞による造血制御に関する研究

Principal Investigator

澤田 賢一 秋田大学, 医学部, 教授 (90226069)

Research Products

[Publications] Yamaguchi M.: "Ex vivo expansion of human UC blood primitive hematopoietic progenitors and transplantable stem cells using human primary BM stromal cells and human AB serum"Cytotherapy. 14. 109-118 (2002)

[Publications] Koizumi K.: "Hemophagocytic syndrome (HPS) in prostatic cancer revealed by disseminated carcinomatosis of the done marrow"J Urology. 168. 1101-1102 (2002)

[Publications] Osawa M.: "Erythroid expansion mediated by Gfi-1B finger protein : role in normal hematopoiesis"Blood. 100. 2769-2777 (2002)

[Publications] Goto H.: "Renal Alpha-Actinin-4 : Purification and puromycin aminonucleoside-binding property"Nephron Exp Nephrol. 93. e27-e35 (2003)

[Publications] Xiao W.: "Tumor necrosis factor-α inhibits generation of glycophorin A+cells by CD34+ cells"Exp Hematol. 30. 1238-1247 (2002)

[Publications] Itoh H.: "Mammalian HSP60 is quickly sorted into the mitochondria under conditions of dehydration"Eur J Biochem. 269. 5931-5938 (2002)

[Publications] Hirokawa M.: "Dsitinct TCRAV and TCRBV repertorie and CDR3 sequence of T lymphocytes clonally expanded in blood and GVHD lesions after human allogeneic bone marrow transplantation"Bone Marrow Transplant. 30. 915-923 (2002)

[Publications] Matsumori M.: "Characterization of the 105-kDa molecular chaperone identification, biochemical properties, and localization"Eur J Biochem. 269. 5632-5641 (2002)

[Publications] Kawabata Y.: "Clinical applications of CD34+ cell-selected peripheral blood stem cells"Therapeutic Apheresis and Dialysis. 7. 298-304 (2003)

[Publications] Koizumi K.: "Severe aplastic anemia associated with thymic carcinoma and partial recovery of hematopoiesis after thymectomy"Ann Hematol. 82. 367-370 (2003)

[Publications] Kawakubo K.: "Granular lymphocyte proliferative disorder after autologous peripheral blood stem cell transplantation for multiple myeloma"Eur J Haematol. 71. 124-127 (2003)

[Publications] Komatsuda A.: "Amyloid A-type renal amyloidosis in a patient with sarcoidosis : report of case and review of the literature"Clinical Nephrology. 60. 284-288 (2003)

[Publications] Fujishima M.: "Amyloid arthropathy resembling seronegative rheumatoid arthritis in a patient with IgD-kappa multiple myeloma"Internal Medicine. 42. 121-124 (2003)

[Publications] Komatsuda A.: "Analysis of mutations in Alpha-Actinin4 and podocin genes of patients with chronic renal failure due to sporadic focal segmental glomerulosclerosis"Renal failure. 25. 87-93 (2003)

[Publications] Lee J.: "Migration and differentiation of nuclear fluorescence-labeled bone marrow stromal cells (BMSCs) after transplantation into cerebral infarct and spinal cord injury in mice"Neuropathology. 23. 169-180 (2003)

[Publications] Saitoh H.: "The presence and longevity of peripherally expanded donor-derived TCR αβ+ mature T lymphocyte clones after allogeneic bone marrow transplantation for adult myeloid leukemias"Leukemia. 17. 1626-1635 (2003)

[Publications] Nimura T.: "Cytogenetic study of 48 patients with multiple myeloma and related disorders"Hematopathol. 43(2). 53-60 (2003)

[Publications] Wakamoto S.: "Biologic activity of RANTES in apheresis PLT Concentrates and its involvement in nonhemolytic transfusion reactions"Transfusion. 43. 1038-1046 (2003)

[Publications] Hirokawa M.: "T-cell repertoire regeneration after human allogeneic hematopoietic stem cell transplantation : Current concept and future direction"Recent Res Devel Immunology. 5. 151-157 (2003)

[Publications] Maki N.: "A nonsense mutation (R220X) in the α-galactosidese A gene causes typical Fabry disease in both genders"Clinical Nephrol. (in press).

[Publications] Ichikawa Y.: "Monitoring the expression profiles of doxorubicin-resistant leukemia cells by serial analysis of gene expression"Int J Hematol. (in press).

[Publications] Miyazaki T.: "73-kDa Molecular chaperone HS73 is a direct target of antibiotic gentamaicin"J Biol Chem. (in press).

[Publications] Fukaya H.: "Co-development of dendritic cells along with erythroid differentiation from human CD34+ cells by tumor necrosis factor-α"Exp Hematol. (in press).

[Publications] Maki N.: "Four novel mutation in the Thiazide-Sensitive Na-Cl cotransporter in Japanese patients with gitelman's sybdrome"Nephrol Dial Transplant. (in press).

[Publications] 澤田賢一, 坊垣暁之, 天崎吉晴, 小池隆夫: "E.自己免疫疾患に対する造血幹細胞移植療法:造血幹細胞 基礎から遺伝し治療・再生医療へ"小澤敏也 編集著,中央医学社. 7 (2002)

[Publications] 小泉和樹, 澤田賢一: "内科領域の輸血,輸血ハンドブック"台2版 霜山龍志 編集,医学書院. 19 (2002)

[Publications] 高橋直人, 澤田賢一: "自家末梢血幹細胞移植よるリンパ腫治療,「癌の臨床」"篠原出版社. 7 (2002)

[Publications] 澤田賢一: "MDSにおける血球分化と増殖の異常"医薬ジャーナル社,血液フロンティア. 9 (2002)

[Publications] 澤田賢一: "知って安心秋田の病気あれこれ"秋田魁新報社. 2 (2003)

[Publications] 澤田賢一: "二次性貧血,改訂第3版「外来診療のすべて」"メジカルビュー社. 2 (2003)

[Publications] 小松田敦, 澤田賢一: "「末梢血幹細胞移植療法」,リウマチ性疾患治療の最前線,内科"南江堂. 4 (2004)

[Publications] 澤田賢一: "幹細胞・造血因子"森真由美 編集,医薬ジャーナル社(印刷中).

[Publications] 澤田賢一: "鉄欠乏性貧血,「血液の事典」"朝倉書店(印刷中).

[Publications] 澤田賢一: "改訂第4版「疾患別最新処方」悪性貧血"メジカルビュー社(印刷中).

澤田賢一秋田大学, 医学部, 教授 (90226069)

[Publications] 澤田賢一, 坊垣暁之, 天崎吉晴, 小池隆夫: "E.自己免疫疾患に対する造血幹細胞移植療法:造血幹細胞基礎から遺伝し治療・再生医療へ"小澤敏也編集著,中央医学社. 7 (2002)

[Publications] 小泉和樹, 澤田賢一: "内科領域の輸血,輸血ハンドブック"台2版霜山龍志編集,医学書院. 19 (2002)

[Publications] 澤田賢一: "幹細胞・造血因子"森真由美編集,医薬ジャーナル社(印刷中).