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 sti mulation with protein A combined with IFN-gamma. The moderate augmentative effect induced by preincubation with protein A was demonstrated to be conce ntration-dependent, whereas IFN-gamma had a very low activating effect Foll owing 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 level s. Thus, tumor cell lysis in the combined system was mediated via TNF-alpha or NO. These results demonstrate the synergistic effects on mouse peritone a macrophage function of protein A in combination with IFN-gamma and sugges t that combinations of such agents may serve as the basis for future in viv o immunotherapy.