Abstract

Dansyl cadaverine, added to human fibroblasts before and during a 1-hr incubation with human interferon (IFN), inhibited the induction of the antiviral state. The inhibitory effect of dansyl cadaverine was rapidly reversible and could not be attributed to either direct inactivation of IFN or to its reduced binding to cells. Of two other amines tested, ammonium chloride caused a small decrease in IFN action, while methylamine was without effect. The transglutaminase inhibitor bacitracin did not significantly reduce IFN action. The effects of methylamine and dansyl cadaverine on lysosomal pH were measured using fluorescein-dextran as a pH indicator. While the increase in lysosomal pH produced by methylamine was large and rapid in onset (1.7 pH units by 10 min), that produced by dansyl cadaverine was smaller and slower in onset (0.5 pH unit by 60 min). Thus, the inhibitory effects of dansyl cadaverine could not be attributed to an alteration in lysosomal pH. Our data show that dansyl cadaverine inhibits IFN action at a step distal to cell surface binding and suggest a role for IFN internalization or receptor recycling.

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