Restoration of lipopolysaccharide-mediated cytotoxic macrophage induction in C3H/HeJ mice by interferon-gamma or a calcium ionophore.

Proteose peptone-induced peritoneal exudate macrophages (PEM) from C3H/HeJ mice do not respond to lipopolysaccharide (LPS) in vitro in terms of activation for tumor cytotoxicity. This unresponsiveness of PEM was overcome by addition of culture supernatant of normal mouse spleen cells stimulated with insoluble concanavalin A. The supernatant component responsible for the restoration of PEM sensitivity to LPS was indicated to be interferon (IFN)-gamma, because pretreatment of the supernatant with anti-mouse IFN-gamma antiserum, but not with anti-IFN-(alpha + beta) antiserum, abolished the supernatant activity and because recombinant murine IFN-gamma (rIFN-gamma) could replace the supernatant effect. Not only the LPS activation of tumor cytotoxicity of PEM but also the sensitivity of PEM to the lethal toxicity of LPS was restored by rIFN-gamma. IFN-gamma action in restoring the LPS responsiveness of PEM was mimicked by a calcium ionophore, A23187, but not by phorbol 12-myristate 13-acetate. These results suggest that IFN-gamma can restore LPS responsiveness of PEM from C3H/HeJ mice and that elevation of the intracellular calcium level is involved in the action of IFN-gamma.