Alpha- and beta-haemoglobin chain induced changes in normal erythrocyte deformability: comparison to beta thalassaemia intermedia and Hb H disease.
The alpha- and beta-thalassaemias are characterized by decreased erythrocyte deformability. To determine what effects excess alpha- and beta-haemoglobin (globin) chains have on cellular and membrane deformability, purified haem-containing alpha- and beta-chains were entrapped within normal erythrocytes. Entrapment of purified alpha-chains in normal erythrocytes resulted in a significant decrease in cellular and membrane deformability similar to that observed in beta-thalassaemia intermedia. The decreased deformability was correlated with alpha-chain membrane deposition, an alteration in membrane proteins and a decrease in membrane reactive thiol groups. These changes in membrane and cellular deformability were time dependent and closely correlated with membrane alpha-chain deposition. The membrane changes and the loss of membrane deformability appeared to account for the loss of cellular deformability in the alpha-chain loaded cells. While both beta-chain loaded and Hb H erythrocytes demonstrated a significant loss of cellular deformability, this loss was less pronounced than in the alpha-chain loaded and beta-thalassaemic cells and may arise from either the increased intracellular viscosity of the beta-chain loaded cells or to the smaller amount of membrane bound globin. In summary, these studies demonstrate that alteration of cellular and membrane deformability occurs very rapidly and as a direct consequence of the autoxidation and membrane binding of the unpaired globin chains.
Scott
M D
MD
Children's Hospital Oakland Research Institute, CA 94609.
Rouyer-Fessard
P
P
Ba
M S
MS
Lubin
B H
BH
Beuzard
Y
Y
D001798:Blood Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004907:Erythrocyte Deformability / Q000502:physiology*; D004909:Erythrocyte Indices / Q000502:physiology; D004910:Erythrocyte Membrane / Q000378:metabolism; D005914:Globins / Q000502:physiology*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D013789:Thalassemia / Q000097:blood*
D001798:Blood Proteins; D006454:Hemoglobins; D005914:Globins