Enhanced macrophage antitumor effects of protein A in combination with IFN-gamma.
In this study we examined the potential for the synergistic augmentation of the antitumor activity of inflammatory mouse peritoneal macrophages by stimulation with protein A combined with IFN-gamma. The moderate augmentative effect induced by preincubation with protein A was demonstrated to be concentration-dependent, whereas IFN-gamma had a very low activating effect. Following preincubation with both protein A and IFN-gamma, a marked enhancement of macrophage activity was noted. In addition, based on the utilization of neutralizing antibody to TNF-alpha or the inhibition of NO production, TNF-alpha and NO were proven to be involved as mediators during the activation of tumoricidal macrophages by protein A in combination with IFN-gamma. We also demonstrated that supernatants from macrophages treated with protein A plus IFN-gamma contained both TNF-alpha and NO at markedly increased levels. Thus, tumor cell lysis in the combined system was mediated via TNF-alpha or NO. These results demonstrate the synergistic effects on mouse peritoneal macrophage function of protein A in combination with IFN-gamma and suggest that combinations of such agents may serve as the basis for future in vivo immunotherapy.
Sungkyunkwan University, College of Pharmacy, Suwon, Korea. snpyo@yurim.skku.ac.kr
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D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007371:Interferon-gamma / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009500:Neutralization Tests; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis; D009573:Nitrites / Q000032:analysis; D013205:Staphylococcal Protein A / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000970:Antineoplastic Agents; D009573:Nitrites; D013205:Staphylococcal Protein A; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma