Effect of ammonium chloride on receptor-mediated uptake of diphtheria toxin by Vero cells

The mechanism of NH₄Cl-mediated protection of Vero cells from diphtheria toxin was studied. In the presence of protective concentrations of NH₄Cl, Vero cells bound, internalized, and degraded radiolabeled diphtheria toxin at the same rate and to the same extent as did the control cells. However, in experiments where specific antibody was added to NH₄Cl-treated cells, a fraction of potentially lethal toxin molecules was maintained in a position accessible to antibody neutralization. This suggests the existence of two processing mechanisms for diphtheria toxin: a non-productive bulk degradation pathway and a productive NH₄Cl-sensitive pathway by which active fragment is eventually delivered to the cytoplasm.