Abstract
Macrophage (Mø) activation for tumoricidal activity can be induced by sequential application of two discrete molecular signals: interferon γ (IFNγ) and endotoxin. The mechanism of signal transduction leading to activation is unclear. Protein kinase C (PKc) has been implicated in cell regulatory functions and as a binding site for phorbol esters. PKc activity was measured in detergent extracts of murine peritoneal Mø before and after treatment with IFNγ. Treatment resulted in a specific 3-4 fold increase in maximal PKc activity. The optimal response occurred at a dose of 1-3 U IFNγ/ml at 3-6 hrs. Inhibition of protein synthesis by cyclohexamide did not prevent this effect. Phorbol binding sites were not affected by IFNγ treatment, and the subcellular localization of PKc was unchanged. Characterization of partially purified enzyme from control and treated Mø demonstrated 1) no direct in vitro activation of PKc by IFNγ, 2) no difference in cofactor (Ca# and phospholipid)requirements, 3) no difference in Km for substrate ATP, 4) increased Vmax in enzyme from treated cells, and 5) enhanced (2-3 fold) response to in vitro phorbols in enzyme from treated cells. These data suggest that the increased PKc activity does not require de novo synthesis of PKc but results from modification of existing PKc leading to enhanced catalytic efficiency. Additionally, we have shown that treatment of Mø with the pharmacologic agents calcium ionophore (A23187) and phorbol myristate acetate mimics the effect of IFNγ on activation. Thus Pkc appears to be an important regulator of Mø activation by IFNγ.
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Becton, P., Hamilton, T., Somers, S. et al. 882 INTERFERON GAMMA MODULATES PROTEIN KINASE C IN MURINE PERITONEAL MACROPHAGES. Pediatr Res 19, 257 (1985). https://doi.org/10.1203/00006450-198504000-00912
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DOI: https://doi.org/10.1203/00006450-198504000-00912