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Characterization and function of antitumor monokines produced by human monocyte-macrophages

Research Project

Project/Area Number 60570292
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionTokushima University School of Medicine

Principal Investigator

SONE SABURO  Tokushima University School of Medicine, Lecturer, 医学部, 助手 (40145024)

Co-Investigator(Kenkyū-buntansha) YOSHIMURA TETSURO  Tokushima University School of Medicine, Associate Prof., 医学部, 助教授 (30035472)
Project Period (FY) 1985 – 1986
Project Status Completed (Fiscal Year 1986)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1986: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1985: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsMacrophages / Monocytes / Antitumor monokines / Human / 腫瘍壊死因子
Research Abstract

The present studies were undertaken to elucidate the effector mechanisms by which activated macrophages kill tumor cells. Human blood monocytes and alveolar macrophages activated to the tumoricidal state produced tumor cytotoxic factor(s)(TCF) into the culture supernatants. The incubation of blood monocytes with suboptimal dose combinations of recombinant gamma interferon and muramyl dipeptide analog generated significant production of TCF, whereas monocytes which were rendered tumoricidal by lipophilic muramyl dipeptide analog encapsulated in multilamellar liposomes, elaborated neither interleukin 1 (IL-1) nor TCF. Human TCF was significantly cytotoxic to 13 of 15 solid-tumor cell lines tested and to 7 of 9 hematopoietic malignant cell lines. Antitumor factors responsible for activated monocyte-mediated tumor cytotoxicity against allogeneic A375 melanoma cells were found to be IL-1 and TCF which had molecular weight of approximately 30,000 by gel filtration. TCF could not be neutralized by treatment with polyclonal anti-IL-1 antibody or anti-tumor necrosis factor (TNF) antibody. Further characterization of this monocyte-derived TCF is required. On the other hand. Liposome membranes composed of phospholipids (phosphatidylcholine and phosphatidylserine) were used to elucidate the molecular mechanisms of action of TNF. TNF induced quick membrane damage of liposomes containing phosphatidylserine at pH values below about 5. Moreover, synergistic effects of TNF and gamma interferon were observed in induction of the membrane damage.

Report

(1 results)
  • 1986 Final Research Report Summary
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Sone,S.: Journal of National Cancer Institute. 74. 583-590 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Sone,S.: Cancer Immunology and Immunotherapy. 21. 93-99 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Sone,S.: Biochimica Biophysica Acta. 823. 227-245 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tandon,P.: Cancer Reserch. 46. 5039-5044 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yoshimura,T.: Journal of Biological Chemistry. 261. (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Sone,S.: "Mcrophage Biology" Alan R.Liss., 355-362 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Sone, S.: "Kinetics and function of tumor cytotoxic factor(s) produced by human blood monocytes activated to the tumoricidal state" Journal of National Cancer Institute. 74. 583-590 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Sone, S.: "Potentiation of direct antitumor cytotoxicity and production of tumor cytolytic factors in human blood monocytes by human recombinant interferon-gamma and muramyl dipeptide derivatives" Cancer Immunology and Immunotherapy. 21. 93-99 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Sone, S.: "Role of alveolar macrophages in pulmonary neoplasias" Biochimica Biophysica Acta. 823. 227-245 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tandon, P.: "Lack of production of interleukin 1 by human blood monocytes activated to the antitumor state by liposome-encapsulated muramyl tripeptide" Cancer Research. 46. 5039-5044 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yoshimura, T.: "Different and synergistic actions of human tumor necrosis factor and interferon- <gamma> in damage of liposome membranes" Journal of Biological Chemistry. 261. (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Sone, S.: Alan R. Liss. Macrophage Biology, 355-362 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary

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Published: 1987-03-31   Modified: 2016-04-21  

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