Activation of Mouse Macrophages for Migration Inhibition and for Tumor Cytotoxicity Is Mediated by Interferon-γ Priming and Triggering by Various Agents

The requirements for activation of C3HeB/FeJ mouse peritoneal macrophages to mediate migration inhibition from capillary tubes was compared with those conditions prerequisite for nonspecific tumor cytotoxicity. Both in vitro assays for macrophage activation were found to require a two-stage process that involved priming by murine recombinant interferon-γ (IFN-γ) and triggering by subactivating concentrations of bacterial lipopolysaccharide (LPS), Lipid A, Polyinosinic-polycytidylic acid (poly I:C), or cobra venom factor (CVF). A dose-related increase in both migration inhibition and tumor cytotoxicity was shown with increasing concentrations of IFN-γ (3.0-50.0 U/ml) in synergistic combination with an LPS trigger. IFN-γ alone produced low levels of migration inhibition or tumor cytotoxicity, only at higher concentrations, that was not attributable to LPS contamination. The concentrations of the various agents required for direct activation or triggering of IFN-γ-primed macrophages were approximately 2- to 10-fold greater for migration inhibition than for tumor cytotoxicity. Our results indicate that the two-signal process of priming and triggering for mediating mouse macrophage nonspecific tumoricidal activity is also operative in migration inhibition from capillary tubes. Thus, under defined conditions with purified lymphokines, the migration inhibition assay appears to be a reliable alternate in vitro correlate of macrophage activation by IFN-γ.