Tumor cytotoxicity of human monocyte membrane-bound interleukin-1 alpha induced by synergistic actions of interferon-gamma and synthetic acyltripeptide, FK-565.
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-gamma (rIFN-gamma), but not other cytokines [rIFN-alpha A, rIFN-beta, 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-gamma and then with FK-565. FK-565 also acted synergistically with rIFN-gamma to stimulate monocytes to produce membrane-associated IL-1 activity, which induced C3H/HeJ thymocyte blastogenesis in response to phytohemagglutinin P. The tumoricidal and thymocyte-stimulating activities of the fixed monocytes were almost completely inhibited by a specific anti-(IL-1 alpha) antiserum, but not by a specific anti-(IL-1 beta) antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated IL-1 alpha of human blood monocytes can be induced by two activation signals (rIFN-gamma then FK-565) at their suboptimal concentrations.
Inamura
N
N
Third Department of Internal Medicine, University of Tokushima School of Medicine, Japan.
Sone
S
S
Okubo
A
A
Kunishige
E
E
Nakanishi
M
M
Ogura
T
T
D000970:Antineoplastic Agents / Q000633:toxicity*; D002460:Cell Line; D004357:Drug Synergism; D005404:Fixatives; D005557:Formaldehyde; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology / Q000633:toxicity*; D008262:Macrophage Activation; D008545:Melanoma / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology / Q000633:toxicity*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides; D011108:Polymers; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000970:Antineoplastic Agents; D005404:Fixatives; D007106:Immune Sera; D007375:Interleukin-1; D008565:Membrane Proteins; D009842:Oligopeptides; D011108:Polymers; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; D007371:Interferon-gamma; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine; C003043:paraform