Abstract
The toxicity of abrin, modeccin, and ricin to Vero cells was maximal at neutral and slightly alkaline pH, and it was strongly reduced at pH 6.0 and below. Diphtheria toxin was most toxic at low pH. Binding and endocytosis of abrin, modeccin, and ricin did not vary much within the pH range tested. High concentrations of the carboxylic ionophore Br-X-537A, protected against all four toxins. Combined treatment of cells with an inhibitor of glycolysis and an uncoupler of oxidative phosphorylation strongly inhibited endocytosis of toxins and protected against intoxication. The protective effect of Ca2+ deprivation, of pH 6.0, and of metabolic inhibitors disappeared soon after transfer of the cells to normal medium, whereas the protective effect of Br-X-537A and of trifluoperazine disappeared slowly. The decay rate of the protection by NH4Cl and by the ionophore A23187 differed with the different toxins. Cells exposed to abrin, modeccin, and ricin under protective conditions which did not inhibit endocytosis of the toxins (Ca2+ deprivation, pH 6.0, Br-X-537A), and then treated with antitoxins to inactivate extracellular toxin, were intoxicated when the protection was released. In contrast, cells exposed to toxins while endocytosis was arrested by treatment with metabolic inhibitors were not intoxicated when antitoxins were added and the metabolic inhibitors removed. Modeccin and diphtheria toxin endocytosed in the presence of trifluoperazine and NH4Cl were unable to intoxicate cells. The possibility that endocytosis is a step in the normal entry route of the toxins is discussed.
Highlights
The toxicity of abrin, modeccin, and ricin to Vero tected from intoxication, can in some cases escape from the cells was maximal at neutral and slightly alkaline pH, vesicles and inhibit protein synthesis, once the protective and it wasstrongly reduced at pH 6.0 and below
Metabolic inhibitors prevented the entry [2].In attempts toelucidate the factors affecting the entry of the plant toxin abrin, modeccin, and ricin, we have in the present paper studied the effect of pH, metabolic inhibitors, as well as ionophores on the sensitivity of cells to these toxins
Ability of Metabolic Inhibitors to Protect against Abrin, Modeccin, Ricin, a n d Diphtheria Toxin-In a previous paper we have shown that the combined treatment with NaN3 and 2-deoxyglucoseprotects cells against diphtheria toxin [2]
Summary
Combined treatment of cells with an inhibitor of glycolysis and an uncoupler of Toxins and Antitoxins-Abrin, abrin A-chain,ricin, and modeccin were prepared as earlier described. The protective effect of Ca2+deprivation, of pH 6.0, and of metabolic inhibitors disappeared soon after transfer of the cells to normal medium, whereas the protective effect of Br-X-637A and of trifluoperazine disappeared slowly. Horse anti-diphtheria toxin was obtained from the National Institute for Public Health, Oslo, Norway. Cells-African green monkey kidney cells (Vero) were obtained from The National Institute for Public Health, Oslo. Cells exposedto toxins while endocytosis was arrested by treatment with metabolic inhibitors were not intoxicated when antitoxins were. Diphtheria toxin endocytosed in the presence of trifluoperazine and NJWl were unable to intoxicate cells.
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