Intracellular Ca 2+ Concentration and Phosphatidylserine Exposure in Healthy Human Erythrocytes in Dependence on in vivo Cell Age

After about 120 days of circulation in the blood stream, erythrocytes are cleared by macrophages in the spleen and the liver. The "eat me" signal of this event is thought to be the translocation of phosphatidylserine from the inner to the outer membrane leaflet due to activation of the scramblase, while the flippase is inactivated. Both processes are triggered by an increased intracellular Ca concentration. Although this is not the only mechanism involved in erythrocyte clearance, in this minireview, we focus on the following questions: Is the intracellular-free Ca concentration and hence phosphatidylserine exposure dependent on the erythrocyte age, i.e. is the Ca concentration, progressively raising during the erythrocyte aging ? Can putative differences in intracellular Ca and exposure of phosphatidylserine to the outer membrane leaflet be measured in age separated cell populations? Literature research revealed less than dozen of such publications with vastly contradicting results for the Ca concentrations but consistency for a lack of change for the phosphatidylserine exposure. Additionally, we performed reanalysis of published data resulting in an ostensive illustration of the situation described above. Relating these results to erythrocyte physiology and biochemistry, we can conclude that the variation of the intracellular free Ca concentration is limited with 10 μM as the upper level of the concentration. Furthermore, we propose the hypothesis that variations in measured Ca concentrations may to a large extent depend on the experimental conditions applied but reflect a putatively changed Ca susceptibility of erythrocytes in dependence of cell age.