THE FORMATION OF TRANSFERRIN RECEPTOR-POSITIVE SICKLE RETICULOCYTES WITH INTERMEDIATE DENSITY IS NOT DETERMINED BY FETAL HEMOGLOBIN CONTENT

Erythrocyte dehydration is an important feature of sickle cell disease , leading to increased sickle hemoglobin polymerization and decreased red blood cell survival, Substantial in vivo dehydration appears to oc cur in reticulocytes or in an even younger subset of reticulocytes tha t are positive for transferrin receptor. Previous studies have suggest ed both sickling-dependent and sickling-independent components of dehy dration for these cells. Two types of investigations are reported here . The first series of experiments explored the possibility that fetal hemoglobin (HbF) content influences the in vivo dehydration of very yo ung, transferrin receptor-positive (T+) cells. These studies confirmed that in most patients the T+ cells in the densest fraction lacked HbF (T+F-). However, T+F- and T+F+ cells appeared to have the same tenden cy to become moderately dense. The second type of investigation examin ed moderately dense T+ cells with normalized K+ content and determined the effect of HbF content on KCl cotransport-mediated dehydration in oxygenated incubations. Under these conditions, both T+F- and T+F+ cel ls had an equal tendency to become more dense by this pathway. Taken t ogether, these studies indicate that at least some young sickle cells become moderately dense due to higher KCl cotransport activity indepen dent of HbF content (and by inference, independent of sickling). Howev er, to become very dense, it appears that further dehydration through a sickling-mediated pathway is required. We suggest that the dehydrati on of young sickle cells occurs in two steps, with the first dominated by KCl cotransport and the second having an important sickling-depend ent component. (C) 1997 by The American Society of Hematology.