Sickling Reversed and Blocked by Urea in Invert Sugar: Optical and Electron Microscopy Evidence

Optical and electron microscopic evidence is presented to support the finding that sickling of hemoglobin S can be reversed and blocked by urea in invert sugar (UIS). Erythrocytes from subjects having hemoglobin SS, AS, or AA were treated with UIS either before or after deoxygenation with sodium metabisulfite (Na2S2O5). Light microscopy studies indicated that approximately one-fifth as much urea is required to block sickling than is necessary to reverse previously sickled poikilocytes to normal forms. Intracellular microfilaments apparent in transmission electron micrographs of sickled erythrocytes were eliminated by treatment of aliquots of the same deoxygenated erythrocytes with UIS. Scanning electron micrographs showed a reversion of sickled poikilocytes to a normal erythrocyte population of biconcave discs. The use of UIS was deduced from Murayama's recently modified hypothesis for the molecular mechanism of sickling which clearly implicates the role of hydrophobic bonds formed between the no. 6 Valine substitution of the beta-S globins and the alpha globins of interacting hemoglobin molecules. The use of UIS to arrest the formation of such hydrophobic bonds is advocated as an evident, safe, and effective therapeutic strategy to treat sickle is advocated as an evident, safe, and effective therapeutic strategy to treat sickle cell crisis. (Author)