Interferon-induced enhancement of macrophage-mediated tumor cytolysis and its difference from activation by lymphokines.
Mouse peritoneal macrophages expressed increased cytolytic activity against tumor cells upon in vitro exposure to partially purified L cell interferon (IFN-beta). In contrast, treatment with human IFN or with mock IFN preparations did not enhance macrophage tumoricidal capacity. Macrophage activation by IFN was optimal with long exposure times and high IFN concentrations. Treatment with polymyxin B sulfate did not affect IFN-induced macrophage cytotoxicity, thus excluding the possibility that bacterial lipopolysaccharide contaminants were responsible for macrophage activation. Conversely, treatment with a highly specific anti-IFN antiserum completely abolished IFN effect on macrophages, but had no effect on lymphokine-induced cytolysis. IFN and the lymphokine macrophage-activating factor (MAF) were compared for their ability to provide the sequence of activation signals to macrophages from the normal responder C3H/HeN mice and from C3H/HeJ mice, which are defective for several macrophage responses. Like MAF, IFN was incapable of inducing tumoricidal activity in C3H/HeJ macrophages. However, whereas MAF provided the first "priming" signal to macrophages of both strains, IFN acted as first signal only for C3H/HeN macrophages, being inactive for cells of the defective C3H/HeJ strain. Furthermore, IFN was not capable of providing the second "expression" signal to "primed" macrophages. These data suggest two different macrophage activation pathways for IFN and MAF.
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D003602:Cytotoxicity, Immunologic; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D007372:Interferons / Q000276:immunology / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000276:immunology; D011112:Polymyxin B / Q000494:pharmacology
D007106:Immune Sera; D008070:Lipopolysaccharides; D008222:Lymphokines; D007372:Interferons; D011112:Polymyxin B