Molecular mechanisms of erythrocyte storage lesion: the role of lipid domains
Biophysics
Final Report Abstract
Red blood cells (RBCs) that are collected for transfusions and stored in PAGGSM can be kept for up to 42 days. During this time, the RBCs undergo changes, so that cells at the end of the storage period differ from cells that are freshly collected. Cells from different donors decay at different rates, for reasons that have not been understood. This project identified a marker indicative of the end-of-storage level of Seite 12 von 12 hemolysis, which is the most important factor in determining whether RBCs are suitable for transfusions. Analysis by mass spectrometry showed that hemolysis was linked to the ratio of POPC (palmitoyl-oleoyl phosphatidylcholine) to SM (sphingomyelin) in the RBC membrane: the ratio is higher at the end of the storage period for cells from high hemolysis donors. This was found to be because of the decrease of SM over the course of the storage period, which can be attributed to the action of sphingomyelinase. The hydrolysis product of SMs, ceramides, are well-known inducers of cell death. The variations in hemolysis between donors may therefore be due to variations in sphingomyelinase activity. The ratio of POPC and SM at the end of the storage period was also higher for RBCs from male donors, and may therefore be the structural cause of the known differences in storage quality for RBCs from male and female donors. Other work from the project showed that hemolysis occurs via both stomatocyte and echinocyte formation, with the result that morphology is a not a good indicator of hemolysis levels when RBCs collected from different donors and stored in PAGGSM are compared. Analysis of the dynamic changes during early stages of echinocyte formation showed that the spicules can move across the cell surface and can split apart into daughter pairs, behaviour that can be more readily explained if the spicules are associated with lipid domains. The well-defined shape changes occurring during the spicule splitting provide for estimating the line tension associated with the putative lipid domains.
Publications
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Flow morphometry to assess the red blood cell storage lesion. Cytometry A. 2017;91(9):874-882
Sierra F DA, Melzak KA, Janetzko K, Klüter H, Suhr H, Bieback K, Wiedemann P
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The Blood Bag Plasticizer Di- 2-Ethylhexylphthalate Causes Red Blood Cells to Form Stomatocytes, Possibly by Inducing Lipid Flip-Flop. Transfus Med Hemother. 2018;45(6):413-422
Melzak KA, Uhlig S, Kirschhöfer F, Brenner-Weiss G, Bieback K
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Hemolysis pathways during storage of erythrocytes and interdonor variability in erythrocyte morphology. Transfus Med Hemother 2020
Melzak KA, Spouge JL, Boecker C, Kirschhöfer F, Brenner-Weiss G, Bieback K
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Lipid ratios as a marker for red blood cell storage quality and as a possible explanation for donor gender differences in storage quality. Vox Sang 2020
Melzak KA, Muth M, Kirschhöfer F, Brenner-Weiss G, Bieback K
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Spicule movement on RBCs during echinocyte formation and possible segregation in the RBC membrane. BBA Biomembranes 2020;1862(10)
Melzak KA, Moreno-Flores S, Bieback, K
