Primary amines and chloroquine inhibit cytotoxic responses to Shigella toxin and permit late antibody rescue of toxin treated cells

Abstract

The effect of lysosomotrophic agents and primary amine inhibitors of transglutaminase on Shigella toxin activity in HeLa cells was determined by measuring cytotoxicity and late antibody rescue. All agents tested resulted in significant antibody rescue, but only ammonium chloride, dansylcadaverine, putrescine, bacitracin, serine/borate buffer, and chloroquine were inhibitory in the absence of added antibody. These compounds appear to be acting within the endocytic vacuole and/or inhibiting translocation of toxin from the cell surface to the cytosol. These data are consistent with a mechanism of translocation of ST from the cell surface to the cytosol by the process of receptor mediated endocytosis.