Storage of Erythrocytes Induces Suicidal Erythrocyte Death

• Published in: Cellular physiology and biochemistry Vol. 39; no. 2; pp. 668 - 676
• Main Authors: Lang, Elisabeth, Pozdeev, Vitaly I., Xu, Haifeng C., Shinde, Prashant V., Behnke, Kristina, Hamdam, Junnat M., Lehnert, Erik, Scharf, Rüdiger E., Lang, Florian, Häussinger, Dieter, Lang, Karl S., Lang, Philipp A.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01-01-2016
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Biological Transport - drug effects; Blood Preservation - methods; Calcium; Calcium - metabolism; Cell Death - drug effects; Cell Death - physiology; Cell volume; Eryptosis - drug effects; Eryptosis - physiology; Erythrocytes - chemistry; Erythrocytes - cytology; Erythrocytes - metabolism; Erythropoietin; Erythropoietin - pharmacology; Flow Cytometry - methods; Fluoresceins - chemistry; Humans; Intracellular Space - metabolism; Mice, Inbred C57BL; Original Paper; Phosphatidylserine; Phosphatidylserines - metabolism; Red blood cell concentrates; Succinimides - chemistry; Time Factors; Red blood cell concentrates; Calcium; Erythropoietin; Cell volume; Phosphatidylserine
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000445657

Background/Aims: Similar to apoptosis of nucleated cells, red blood cells (RBC) can undergo suicidal cell death - called eryptosis. It is characterized by cell shrinkage and phosphatidylserine translocation. Eryptosis is triggered by an increase of intracellular calcium concentration due to activation of nonselective cation channels. The cation channels and consequently eryptosis are inhibited by erythropoietin. Eryptotic RBC are engulfed by macrophages and thus rapidly cleared from circulating blood. In this study, we explored whether storage of RBC influences the rate of eryptosis. Methods: Flow cytometry was employed to quantify phosphatidylserine exposing erythrocytes from annexin V binding and cytosolic Ca 2+ activity from Fluo-3 fluorescence. Clearance of stored murine RBC was tested by injection of carboxyfluorescein succinimidyl ester (CFSE)-labelled erythrocytes. Results: Storage for 42 days significantly increased the percentage of phosphatidylserine exposing and haemolytic erythrocytes, an effect blunted by removal of extracellular calcium. Phosphatidylserine exposure could be inhibited by addition of erythropoietin. Upon transfusion, the clearance of murine CFSE-labelled RBC from circulating blood was significantly higher following storage for 10 days when compared to 2 days of storage. Conclusion: Storage of RBC triggers eryptosis by Ca 2+ and erythropoietin sensitive mechanisms.