Erythrocyte membrane defects and asymmetry in paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome.
Paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplastic syndromes (MDS) are clonal disorder of haematopoietic stem cells that may eventually lead to chronic anemia. The ultrastructural defects in erythrocyte membranes may have a role in early red cell destruction within circulation. The lifespan of the erythrocyte primarily correlates to externalization of phosphatidylserine (PS) and loss of glycophorins from the erythrocyte surface. The span of survival of mature erythrocytes in the circulation in case of MDS and PNH is yet unclear and has been studied by measuring simultaneous exposure of PS and loss of glycoconjugates, primarily glycophorins from membrane surface. The extent of the loss of PS asymmetry and cell surface glycophorins in density separated erythrocytes of six MDS and three PNH patients has been probed by fluorochrome conjugated annexin V and wheat germ agglutinin using flow cytometry. The cells with lighter density showed a higher amount of PS on the outer surface compared to those of heavier cells in all PNH and MDS cases, showing the opposite trend to that observed in normal erythrocytes. In addition, the lighter cells had more cell surface glycophorins compared to heavier cells in all the cases. Such lowering of glycophorin levels from the lighter to heavier cells was maximum in refractory anaemia (RA) and minimum in the normal cells studied. Greater loss of PS asymmetry and cell surface glycophorin in the lighter or younger erythrocytes together could be responsible for their faster destruction and removal (eryptosis) in PNH and MDS.
Basu
Sumanta
S
Structural Genomics Section, Saha Institute of Nuclear Physics, Kolkata, India.
Banerjee
Debasis
D
Ghosh
Malay
M
Chakrabarti
Abhijit
A
D000328:Adult; D000368:Aged; D000753:Anemia, Refractory / Q000097:blood / Q000378:metabolism / Q000473:pathology; D002469:Cell Separation; D002499:Centrifugation, Density Gradient; D002648:Child; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000473:pathology*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006021:Glycophorins / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D010718:Phosphatidylserines / Q000378:metabolism; D013499:Surface Properties
D006021:Glycophorins; D010718:Phosphatidylserines