1986 Fiscal Year Final Research Report Summary
Characterization and function of antitumor monokines produced by human monocyte-macrophages
| Project/Area Number |
60570292
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Tokushima University School of Medicine |
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Principal Investigator |
SONE SABURO Tokushima University School of Medicine, Lecturer, 医学部, 助手 (40145024)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA TETSURO Tokushima University School of Medicine, Associate Prof., 医学部, 助教授 (30035472)
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| Project Period (FY) |
1985 – 1986
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| Keywords | Macrophages / Monocytes / Antitumor monokines / Human / 腫瘍壊死因子 |
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| 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.
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