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Tumor cytotoxicity of human monocyte membrane-bound interleukin-1α induced by synergistic actions of interferon-γ and synthetic acyltripeptide, FK-565

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Summary

Human blood monocytes were isolated by counter-flow centrifugal elutriation from healthy donors and these noncytotoxic monocytes were rendered tumoricidal to allogeneic melanoma (A375) cells by activation with a synthetic acyltripeptide (FK-565), as assessed by measuring release of [125I]iododeoxyuridine in 72 h. When monocytes were treated with FK-565 for 16 h, and then fixed with paraformaldehyde, they showed cytotoxicity to A375 melanoma cells. The fixed-monocyte-mediated cytotoxicity to A375 cells was induced by the synergistic actions of FK-565 and recombinant interferon-γ (rIFN-γ), but not other cytokines [rIFN-αA, rIFN-β, tumor necrosis factor (TNF), interleukin (IL)-2, -3 and -6]. For synergistic activation of monocytes with induction of a membrane-associated antitumor monokine, the monocytes had to be incubated first with rIFN-γ and then with FK-565. FK-565 also acted synergistically with rIFN-γ to stimulate monocytes to produce membrane-associated IL-1 activity, which induced C3H/HeJ thymocyte blastogenesis in response to phytohemagglutinin P. The tumoricidal and thymocytestimulating activities of the fixed monocytes were almost completely inhibited by a specific anti-(IL-1α) antiserum, but not by a specific anti-(IL-1β) antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated IL-1α of human blood monocytes can be induced by two activation signals (rIFN-γ then FK-565) at their suboptimal concentrations.

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Abbreviations

IL:

interleukin

IFN:

interferon

TNF:

tumor necrosis factor

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Authors and Affiliations

  1. Third Department of Internal Medicine, The University of Tokushima School of Medicine, Kuramoto-cho, 770, Tokushima, Japan

    Noriaki Inamura, Saburo Sone, Akio Okubo, Eiji Kunishige, Mie Nakanishi & Takeshi Ogura

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  1. Noriaki Inamura
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  2. Saburo Sone
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  3. Akio Okubo
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  4. Eiji Kunishige
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  5. Mie Nakanishi
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  6. Takeshi Ogura
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Inamura, N., Sone, S., Okubo, A. et al. Tumor cytotoxicity of human monocyte membrane-bound interleukin-1α induced by synergistic actions of interferon-γ and synthetic acyltripeptide, FK-565. Cancer Immunol Immunother 28, 164–170 (1989). https://doi.org/10.1007/BF00204984

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  • DOI: https://doi.org/10.1007/BF00204984

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