Cellular and membrane properties of alpha and beta thalassemic erythrocytes are different: implication for differences in clinical manifestations.
To define how excess unpaired alpha- and beta-globin chains in severe beta-thalassemia and severe alpha-thalassemia interacting with the membrane might alter cellular and membrane properties, we performed a series of biophysical and biochemical analyses on erythrocytes obtained from affected patients. Detailed analysis of cellular and membrane deformability characteristics showed that both forms of thalassemic erythrocytes have excess surface area in relation to cell volume and increased membrane dynamic rigidity. The deformability characteristics of thalassemic erythrocytes in hypertonic media differed significantly from that of normal erythrocytes of identical cell density. These findings suggest that dynamic rigidity of thalassemic erythrocytes is influenced not only by cytoplasmic viscosity determined by cell hemoglobin concentration but also by the extent and type of globin interacting with the membrane. In contrast to the above-noted similarities, major differences were noted in the mechanical stability of the alpha- and beta-thalassemic membranes and in their state of cell hydration. While the mechanical stability of alpha-thalassemic membranes was normal or marginally elevated, the stability of beta-thalassemic membranes was markedly decreased to half the normal value. Cell-density analysis showed that the alpha-thalassemic erythrocytes were uniformly less dense than normal, while beta-thalassemic erythrocytes had a broad-density distribution, with all populations having both lower and higher than normal density values, implying cellular dehydration in beta-thalassemia and not in alpha-thalassemia. Membrane-protein analysis revealed that excess globin chains were bound to the membrane skeletons of both alpha- and beta-thalassemic erythrocytes, with the highest amounts being found in membrane skeletons derived from erythrocytes of splenectomized individuals with beta-thalassemia intermedia. These data demonstrate that interaction of excess alpha- and beta-globin chains with membranes produces different cellular changes and suggest that the observed differences in the pathophysiology of alpha- and beta-thalassemias may be related to different cellular effects induced by the excess in beta- and alpha-globin chains.
Schrier
S L
SL
Department of Medicine, Stanford University, CA.
Rachmilewitz
E
E
Mohandas
N
N
D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D004907:Erythrocyte Deformability; D004910:Erythrocyte Membrane / Q000502:physiology*; D005914:Globins / Q000502:physiology*; D006801:Humans; D009996:Osmotic Fragility; D012212:Rheology; D013156:Splenectomy; D013789:Thalassemia / Q000097:blood*
D001457:Anion Exchange Protein 1, Erythrocyte; D005914:Globins