Analysis of the primed intermediate stage in the macrophage tumoricidal activation pathway

Model systems were developed for the analysis of macrophage activation for tumor cell killing using established murine macrophage-like tumor cell lines. This activation process is currently understood as consisting of sequential priming and triggering steps. Treatment with interferon-gamma resulted in the acquisition of a primed activation state by some, but not all, of the macrophage populations studied. A dissociation of the modulation of cell surface major histocompatibility complex (MHC) Class II (Ia) antigen expression and priming for tumor cytolysis by interferon-gamma was observed in the macrophage cell lines, indicating that the primed intermediate in the macrophage tumoricidal activation pathway was not necessarily Ia antigen-positive. Examination of the tumor cytolytic activity of cycloheximide-treated cells indicated that protein synthesis was required for priming by interferon-gamma. A novel priming stimulus, gamma irradiation, was identified using the RAW 264.7 cell line. Treatment of the RAW 264.7 cell line with doses of gamma radiation > 1000 rads resulted in the acquisition of the primed intermediate activation state, as evidenced by the expression of maximum tumor cell killing following incubation of irradiated cells with the triggering stimulus alone