sq-23377 and Sickle-Cell-Trait

Normally, human erythrocytes display several responses to elevated intracellular calcium levels. These include a shape transition from discocyte to spherocyte, shedding of microvesicles into the extracellular fluid, and enhanced susceptibility to the hydrolytic action of secretory phospholipase A(2). These responses to elevated intracellular calcium were all blunted in erythrocytes containing hemoglobin S. The reduction of both the shape transition and the shedding of microvesicles were greater than the impairment of phospholipase susceptibility, and both correlated strongly with the intracellular content of hemoglobin S. In contrast to the response to elevated intracellular calcium, erythrocytes containing hemoglobin S displayed a 2.5-fold increase in basal susceptibility to phospholipase A(2) compared to control erythrocytes in the absence of ionophore. The effect was more prominent among samples from patients heterozygous for hemoglobin S than in samples from homozygous individuals. These results reveal additional abnormalities in the membranes of sickle cell erythrocytes beyond those described previously and demonstrate that red blood cells from both heterozygous and homozygous are affected. Furthermore, they suggest a possible means by which sickle cell disease and trait patients may display enhanced vulnerability to inflammatory stimuli.

Topics: Anemia, Sickle Cell; Calcium; Erythrocyte Membrane; Fatty Acids; Hemoglobin, Sickle; Humans; Hydrolysis; Ionomycin; Kinetics; Light; Phospholipases A; Scattering, Radiation; Sickle Cell Trait; Spectrometry, Fluorescence