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Analysis of heat shock protein 70 as a causal molecule of aplastic anemia

Research Project

Project/Area Number 09671103
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKanazawa University

Principal Investigator

NAKAO Shinji  University Hospital, Kanazawa University Assistant Professor, 医学部・附属病院, 講師 (70217660)

Co-Investigator(Kenkyū-buntansha) SATOH Noriyuki  Sapporo Medical University, Professor, 医学部, 教授 (50158937)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsaplastic anemia / heat snock protein 72 / cyclosporine / antithymocyte globulin / heat shock protein72 / hsp70-2
Research Abstract

To characterize immune pathophysiology of aplastic anemia (AA), we studied expression of heat shock piotein (-hsp) 72 in peripheral blood mononuclear cells (PBMCs) of untreated AA patients using flow cytometry. AA patients whose PBMCs exhibited high percentages (>30%) of hsp72+ cells after heat treatment were likely to respond to cyclosporine therapy. The high inducibility of hsp72 in PBMCs was not detected in other hematologic diseases, such as myelodysplastic syndrome and hemolytic anemia. Among PBMCs of AA patients responsive to cyclosporine, hsp72 expression was primarily detected in T cells. Thus, detection of hsp72^+ cell in PBMCs before treatments appeared to be useful for predicting a favorable response to cyclosporine therapy. Next, we collected PBMCs of AA patients who later received combined immunosuppressive therapy consisting of antithymocyte globulin and cyclosporine from the other hospitals in Japan, and determined the inducibility of hsp72. Although approximately 40% of … More patients showed high percentages of hsp72^+ cell among PBMCs, there was no correlation between a good response to the combined immunosuppressive therapy and a high inducibility of hsp72 in PBMCs.
In some AA patients, hsp72 was detectable not only in the cytoplasm of PBMCs but also on the surface of red blood cells (RB Cs). Detailed analysis of hsp72 on RBCs revealed that in additi9n to AA patients, hsp72^+ cells could be detected on 20-90% of RBCs of about 30% of normal individuals and that its expression was restricted to individuals bearing blood type A and AB.Heat treatments did not influence the expression of hsp72 on RB Cs. Since hsp72 could not be detected on normocytic erythroblasts that were generated from erythroid progenitor cells of a normal individual with blood type A, hsp72 appeared to emerge on RBCs after terminal differentiation of erythroid progenitor cells. Beside hsp72, RBCs of individuals with blood type A and AB expressed hsp90. Binding of anti-hsp72 monoclonal antibodies was not seen in type O RBCs that were forced to express A antigens by the treatment with N-acetyl galactosaminyltransferase and UDP-N-acefyl galactosamine. Thus, the expression of hsp72 seemed to be genetically determined although it is closely associated with A antigen expression. The function and biological significance of hsp72 on RBCs remain to be determined. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Nakao S,et al.: "Isolation of a T-cell clone showing HLA-DRB1 0405-restricted cytotoxictty for hematopoietic cells in a patient with aplastic anemia." Blood. 89. 3691-3699 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] SuS,et al.: "Inhibition of immature erythroid progenitor cell proliferation by macrophage inflammatory protein-lalpha by interacting mainly with a c-c chemokire receptor, CCRI." Blood. 90. 605-611 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takami A, Nakao S,et al.: "Successful therapy of myelody splastic syndrome with menatetrenone, a vitamin K2 analog." Int J Hematol. 69. 24-26 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takami A,Nakao S,et al.: "Impaired response of granulocyte-committed progerltor cells to stem cell factor and grarulocyte colony-stimulating factor in human cyclic revtropenia." Ann Hematol. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zeng W,Nakao S,et al.: "Characterization of T-cell repertoire in the bore marrow of immune-mediated aplastic anemia; evidence for the involvement of antigen-driver T cell response in cyclosporire-dependent aplastic aremia." Blood. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chuhio T,Nakao S,et al.: "Successful treatment of persistent erythroid aplasia caused by parvovirus B 19 infection in a patient with variable immunodeficiency with low-dose immunoglobuli〓" Am J Hematol. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 中尾 真二、他: "再生不良性貧血患者骨髄における V_B15+ T細胞クロノタイプの相同性" 厚生省特定疾患に関する免疫研究班平成8年度・研究業績報告書. 27-29 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 中尾 真二、他: "再生不良性貧血における免疫学的機序の多様性:シクロスポリン反応例における骨髄T細胞レパトアの解析" 厚生省特定疾患に関する免疫研究班 平成9年度研究業績報告書. 28-31 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 中尾 真二: "Arrval Review 血液 1997 (高久 史磨、宮崎 澄雄、斉藤 英彦、溝口 英昭、坂田 洋一編)" 中外医学社,東京, (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 中尾 真二: "最新内科学大系 プログレス3 血液・造血器疾患 (井村 裕夫、尾形 悦郎、高久 史磨、垂井 清一郎 編)" 中山書店,東京, (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 中尾 真二,松田 保: "別冊 日本臨床 血液症候群 I" 日本臨床社,大阪, (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 中尾 真二: "KEY WORD 1998-2000 血液 (溝口 秀昭,浦部 晶夫,斉藤 政樹,中川雅夫 編)" 先端医学社,東京, (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 中尾 真二: "内科学 (黒川 清,松澤 佑次 編集主幹)" 文光堂,東京印刷中, (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 中尾 真二: "免疫抑制薬の選び方と使い方 (三森 経世 編)" 南江堂,東京印刷中, (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shinji Nakao: "Aplastic anemla-pathophy siology, epidemiology, clinical presentation and treatment (Editors : Schrezenmeier H, Bacigalvpo A)" Cambridge University Press, London in press,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takami A,Nakao, S,et al.: "High inducibility of heat shock protein 72 (hsp72) in peripheral blood mononuclear cells of aplastic anemia patients : A reliable marker of immune-mediated aplastic anemia responsive to cyclosporine therapy." Br J Haematol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zeng WH,Nakao S,et al: "Characterization of T-cell repertoire in the bone marrow of immune-mediated aplastic anemia:evidence for the involvement of antigen-driren T cell response in cyclosporine-dependent aplastic anemia" Blood. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] 中尾真二: "免疫学的骨髄障害の機序と治療" 日本医師会雑誌. 120. 43-46 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中尾真二: "薬の効くメカニズム:再生不良性貧血に対する免疫抑制療法" 今月の治療. 6. 75-79 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中尾真二: "再生不良性貧血の病態" 日常診療と血液. 8. 13-19 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中尾真二: "抗原特異的T細胞と再生不良性貧血" 臨床血液. (印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] 中尾真二: "再生不良性貧血の発症機序" 臨床医. 24. 1000-1002 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中尾真二,松田保: "別冊日本臨床 血液症候群:I" 日本臨床社,大阪, 14-17 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中尾真二: "KEY WORD 1998-2000 血液 溝口秀昭,浦部晶夫,斉藤政樹,中川雅夫,編" 先端医学社,東京, 106-107 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakao S.: "Early establishment of hematopoletic chimerism following allogeneic peripheral blood stem cell transplantation in comparison with allogeneic bone marrow transplantatic" Biol Blood Marrow Transplant. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakao S.: "Induction of autocytotoxic T cells with cyclosporine and interferon-γ for patients with non-Hodgkin's lymphoma after transplantation of peripheral blood stem cells" J Allergy Clin Immunol. 100. S65-S69 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakao S.: "Isolation of a T-cell clone showing HLA-DRBI^*0405-restricted cytotoxicity for hematopotetic cells in a patient with aplastic anemia." Blood. 89. 3691-3699 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakao S.: "Immune mechanism of aplastic anemia." Int Hematol. 66. 127-134 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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