OBSERVATIONS ON MECHANISM OF ERYTHROCYTE SICKLING

Extract: Recent studies have shown that the fundamental mechanism underlying the distortion of sickled erythrocytes is the conversion of reduced sickle cell hemoglobin (HbS) into rods. The abnormal molecules appear to stack into 65 Å filaments that, through parallel association, form twisted rods 180–190 Å in diameter. In the present investigation, the effect of hemolysis on parallel bundles of rods in sickled cells has been examined. Hemolysis was found to destroy the framework of rods in the reverse stages of formation. The rods broke down into filaments, which disappeared into amorphous debris. To further characterize the nature of the sickling phenomenon, the structure of hemoglobin crystals formed in canine erythrocytes by freeze-thaw was examined. The structure differed significantly from rods of sickled hemoglobin. Results of these investigations support the concept that sickling is a process of sol-gel transformation, not of intracellular crystallization. Speculation:Precise arrangement of HbS molecules in the rods formed when intact erythrocytes sickle under reduced oxygen tension has not been defined. The phenomenon of stacking of HbS molecules into 65 A filaments before aggregation of the 170–190 Å rods is supported by this study. It is not certain, however, whether the rod is an aggregate of twisted filaments like the microtubule, or an ascending filamentous spiral of molecular subunits resembling tobacco mosaic virus. Clarification of the molecular arrangement is important for understanding the mechanism of sickling and essential for the selection of chemical agents potentially capable of disassembling or preventing formation of rods of HbS. © International Pediatrics Research Foundation, Inc. 1969. All Rights Reserved.