Differential sensitivity of reticulocytes to nicked and unnicked diphtheria toxin

Abstract

The effects of diphtheria toxin (DT) on rabbit reticulocytes were studied. Protein synthesis of the cells was inhibited at relatively high DT concentrations. Several drugs including metabolic inhibitors, nucleotides and amines blocked DT-induced toxicity in reticulocytes in a manner comparable to their known protective effects in other cell lines. This suggested that receptor-mediated binding and internalization of DT occurred in reticulocytes. Highly purified unnicked DT did not inhibit protein synthesis, while nicked toxin was effective. Treatment of the unnicked toxin with trypsin converted it into a potent form. It is hypothesized that reticulocytes lack the required toxin-activating (nicking) enzyme or that the putative enzyme is not located on or in the cell in a manner where it can interact with the toxin.