Tin triggers suicidal death of erythrocytes

Suicidal erythrocyte death or eryptosis is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure at the erythrocyte surface. Triggers of eryptosis include increase in cytosolic Ca(2+) activity, formation of ceramide and energy depletion. Excessive eryptosis contributes to several anemic conditions. Intoxication with inorganic tin(II) may lead to anemia. The present study therefore explored whether tin influences eryptosis. To this end, erythrocytic phosphatidylserine exposure was estimated from annexin V-binding, cell volume from forward scatter, cytosolic Ca(2+) activity from Fluo3 fluorescence, ceramide formation from binding of fluorescent antibodies and cytosolic ATP utilizing a luciferin-luciferase assay kit. Under control conditions, eryptosis was observed in less than 5% of the erythrocytes. Exposure to tin (1-100 microm) significantly increased the percentage of PS-exposing erythrocytes and decreased cell volume. The effect was paralleled by an increase in the cytosolic Ca(2+) concentration, ceramide formation and a decrease of intracellular ATP concentration. In conclusion, tin triggers eryptosis, an effect at least partially due to Ca(2+ )entry, ceramide formation and ATP depletion. The effect could contribute to tin-induced anemia.