Acid pH induces formation of dense cells in sickle erythrocytes

When erythrocytes from patients homozygous for hemoglobin S (SS) are swollen or exposed to pH less than 7.40, they lose K, Cl, and water through a volume and pH-dependent KCl cotransport system. We report that carbon monoxide-treated SS cells become progressively denser when incubated for eight to 12 hours in media with pH less than 7.40 (7.3 to 7.0) at constant cell 2,3-diphosphoglycerate (DPG). This phenomenon is maximal in fresh SS cells from the top and middle density fractions, and is absent in cells from the densest fraction. When AA cells are separated according to density, acid pH induces cell shrinkage in the least dense fraction of AA cells, which has considerable KCl cotransport, but produces no change in cell density in the densest fractions of AA erythrocyte, which have no KCl cotransport. These data suggest that dense cells can form in oxygenated SS erythrocytes when the KCl cotransport system is activated by acidification.