Analysis of deficiencies in IFN-γ-mediated priming for tumor cytotoxicity in peritoneal macrophages from A/J mice

The functional and biochemical responses of macrophages derived from the A/J mouse strain to IFN-γ have been studied. As compared to macrophages obtained from C57BL/6 strain mice, cells from mice of the A/J strain are deficient in their response to IFN-γ for acquisition of tumoricidal competence. This deficiency was not due to reduced expression of surface receptors for IFN-γ or to altered affinity of the receptor for its ligand. IFN-γ recently has been shown to enhance the potential activity of protein kinase C (PKc) and to modulate the efflux of intracellular Ca²⁺ in macrophages from C57BL/6 mice. Neither of these two biochemical changes were induced in macrophages derived from A/J mice. Functional competence could, however, be pharmacologically induced in both C57BL/6- and A/J-derived macrophages by combined treatment with an ionophore plus phorbol myristic acetate, which increase intracellular Ca²⁺ and stimulate PKc, respectively. Although the exact nature of the deficit in A/J strain mice has not been defined, the present findings indicate that it lies between the expression of receptor and the modulation of PKc activity and Ca²⁺ levels. Furthermore, the data provide support for the notion that these molecular changes are important components of the stimulus-response coupling process in IFN-γ-mediated activation of macrophages.