We are reporting in vitro observations of sickle-unsickle transformation of freely suspended single cells (HbSS) induced by oxygenation-deoxygenation. The events were recorded by cinematography (phase optics, 16 mm cinematography). In addition, cells were fixed after progressive increments of oxygenation for subsequent scanning-beam electron microscopy. These studies seem to warrant the followi...

Initially, the pathophysiology of sickle cell anemia was attributed to deoxygenation-induced polymerization of a mutant form of hemoglobin, hemoglobin S, as well as sickling of red blood cells that plug blood vessels causing the onset of a painful vasoocclusive crisis. Although hemoglobin S polymerization is central to the pathophysiology of this disease, the initiation of a vasoocclusive episo...

A B S T R A C T Although pyridoxal phosphate is known to inhibit gelation of purified hemoglobin S, antisickling activity has never been demonstrated for intact erythrocytes. We incubated washed erythrocytes at 370C either in buffer alone, or with added pyridoxal phosphate or pyridoxal, washed these cells, suspended them in untreated buffer, and compared the percent modified hemoglobin, the oxy...

The ultrasonic absorption of sickle cells was compared with the morphological changes in these cells are produced by varying oxygen tensions and pH. A decrease in oxygen tension caused increased sickling and an increase in the ultrasonic absorption of the blood. An increase in pH reduced the ultrasonic absorption and decreased sickling. These findings indicate that ultrasonic absorption can det...

Sickling-induced cation fluxes contribute to cellular dehydration of sickle red blood cells (SS RBCs), which in turn potentiates sickling. This study examined the inhibition by dipyridamole of the sicklinginduced fluxes of Na1, K1, and Ca11 in vitro. At 2% hematocrit, 10 mM dipyridamole inhibited 65% of the increase in net fluxes of Na1 and K1 produced by deoxygenation of SS RBCs. Sickle-induce...

In sickle cell disease, intravascular sickling and attendant flow abnormalities underlie the chronic inflammation and vascular endothelial abnormalities. However, the relationship between sickling and vascular tone is not well understood. We hypothesized that sickling-induced vaso-occlusive events and attendant oxidative stress will affect microvascular regulatory mechanisms. In the present stu...

To develop an animal model for sickle cell anemia, we have created transgenic mice that express a severe naturally occurring human sickling hemoglobin, Hb S Antilles. Due to its low solubility and oxygen affinity, Hb S Antilles has a greater propensity to cause red cell sickling than Hb S. To make transgenic animals that express a high level of Hb S Antilles, the erythroid-specific DNAse I hype...

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 occur in reticulocytes or in an even younger subset of reticulocytes that are positive for transferrin receptor. Previous studies have suggested both sickling-dependent and sickling-indepen...