Concanavalin A-induced inhibition of abrin and ricin activity parallels with a decrease of the number of toxin-binding uptake-elution cycles

Abstract Treatment of either Friend leukemia cells (FLC) or HeLa cells with concanavalin A (conA) causes a significant reduction of abrin and ricin activity. In order to elucidate the mechanism of this phenomenon, the toxin uptake and release were studied. ConA-treated cells show an increase of toxin bulk uptake, but a marked decrease of toxin entry into the cytosol. Analysis of toxin elution into the medium has demonstrated that conA induces a reduction of the toxin excretion process from the cell membrane. No significant degradation of either internalized or released toxin has been detected either in conA-treated or in untreated cells. Moreover, the toxin released into the medium is still biologically active. Treatment of cultures with lactose, in conditions which inhibit de novo binding of eluted toxin, determines a protective effect on the ricin and abrin activity; this phenomenon resembles the conA-induced protective effect. Our results suggest that conA decreases the number of toxin binding uptake-elution cycles, causing thereby a lower probability of toxin entry into the cytoplasm as compared to control cells.