Zinc-induced suicidal erythrocyte death

Background: Zn2+ stimulates secretory sphingomyelinase, which in turn produces ceramide, an important trigger of suicidal erythrocyte death or eryptosis. Eryptosis is characterized by exposure of phosphatidylserine (PS) at the erythrocyte surface and by cell shrinkage. As macrophages are equipped with PS receptors, they bind, engulf, and degrade PS-exposing cells. Objective: We examined whether Zn2+ stimulates ceramide formation and PS exposure of erythrocytes and thus may be able to trigger suicidal erythrocyte death. Design: In erythrocytes from healthy volunteers, PS exposure (Annexin V binding), cell volume (forward scatter), cytosolic Ca2+ activity (Fluo3 fluorescence), and ceramide formation (anticeramide antibody) were determined by fluorescence-assisted cell sorting. Results: Exposure to Zn2+ (>= 25 mu mol/L Zn2+) significantly increased annexin binding. The effect was paralleled by increase of cytosolic Ca2+ activity (>= 25 mu mol/L Zn2+) and by ceramide formation (>= 10 mu mol/L Zn2+). Glucose depletion (24 h) similarly increased PS exposure, an effect significantly enhanced in the presence of Zn2+ (>= 10 mu mol/L Zn2+). Conclusion: Zn2+ triggers suicidal erythrocyte death, an effect partially due to ceramide formation and an increase of cytosolic Ca2+ activity.