Modulation of tumoricidal activity, induced in bone-marrow-derived mononuclear phagocytes by interferon gamma or Corynebacterium parvum, by interferon beta, tumor necrosis factor, prostaglandin E2, and transforming growth factor beta.
Among a series of agents, including various interleukins and growth factors, only interferon gamma (IFN gamma) and heat-killed Corynebacterium parvum (CP) organisms were able to elicit, within 24 hr, tumoricidal activity in bone-marrow-derived mononuclear (BMM) phagocytes. In subsequent experiments, the abilities of interferon beta (IFN beta), tumor necrosis factor alpha (TNF alpha), prostaglandin E2 (PGE2), and transforming growth factor beta (TFG beta), alone or in combinations of 2, to modulate tumoricidal activity triggered in BMM phagocytes by IFN gamma or CP, were compared. In concentrations secreted by macrophages under physiological conditions, these agents proved potent in modulating induction and/or expression of tumoricidal activity. However, their ability to interfere with tumoricidal activity varied considerably, depending on the extent of macrophage differentiation and/or functional responsiveness, the pathway of macrophage activation, the type, concentration and combination of the macrophage secretory molecules, and on whether the agents were present during induction and expression or only during expression of tumoricidal activity. In showing that IFN beta and TNF alpha were mostly enhancing and TGF beta mostly suppressive, whereas PGE2 suppressed induction but enhanced expression of tumoricidal activity, our findings provide further support for the concept that these macrophage-derived molecules have a key role in autocrine regulation of macrophage functional activities.
Institute for Immunology and Virology, University of Zurich, Switzerland.
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Keller
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Keist
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van der Meide
D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D015232:Dinoprostone / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation; D009369:Neoplasms / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology*; D011425:Propionibacterium acnes / Q000276:immunology*; D051381:Rats; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma; D015232:Dinoprostone