Requirement for protein synthesis for induction of macrophage tumoricidal activity by IFN-alpha and IFN-beta but not by IFN-gamma.

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Abstract
Peritoneal mouse macrophages elicited by proteose-peptone (pM phi) were treated in vitro with IFN-alpha, IFN-beta, or IFN-gamma in the presence or absence of cycloheximide (Cy), a reversible inhibitor of protein synthesis, and were assayed for cytolytic activity against tumor cells. Inhibition of protein synthesis during treatment of pM phi with IFN-alpha or IFN-beta prevented the development of cytotoxic activity. In contrast, IFN-gamma was fully capable of inducing cytotoxic pM phi in the presence of Cy. Moreover, pM phi treated with mixtures of IFN in the presence of Cy were activated for cytotoxicity only by IFN-gamma together with IFN-alpha or IFN-beta, but not by IFN-alpha plus IFN-beta. These results indicate that the activation of pM phi by IFN-gamma is independent of new protein synthesis, whereas the activation of pM phi by IFN-alpha and/or IFN-beta requires active protein synthesis, suggesting that the mechanism of induction of cytotoxic pM phi by IFN-gamma differs from that by the other types of IFN.