In order to study possible alterations in membrane lipids during sickling, we have measured the difference in susceptibility to lipid peroxidation, binding of trinitrobenzenesulfonic acid (TNBS) to aminophospholipids, and fatty acid uptake in cells containing sickle haemoglobin under aerobic and anaerobic conditions. We have also examined TNBS binding in irreversibly sickled cells in an attempt to evaluate the permanent effects of any such alterations. We found that when erythrocytes were sickled by deoxygenation, the susceptibility to lipid peroxidation and binding of TNBS to aminophospholipids was markedly increased, while normal control cells showed no change. These effects appeared to be specific for the sickled state rather than a nonspecific consequence of cell age or the concentration of sickle haemoglobin within the cell. In contrast, fatty acid incorporation into membrane phospholipids, representing potential lipid renewal, was decreased in the sickled state. Cell fractions enriched in irreversibly sickled cells showed increased TNBS labelling in air and only modest rises with anoxia. Taken together, these data imply a rearrangement of membrane lipids during the sickling process and suggest a permanent reorganization of membrane lipids in the irreversibly sickled cell.
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