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.