Evidence for Rapid Loss of Newly Synthesized Haemoglobin S Molecules in Sickle Cell Anaemia and Sickle Cell Trait

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Abstract
Newly completed Hb S molecules rather than free .beta.s-chains are apparently preferentially bound to the reticulocyte stroma of individuals with sickle cell trait and sickle cell anemia. Reticulocytes from individuals with HbAA, AS and SS were incubated with [3H]leucine from 1.25 min to 120 min. Unlike the stroma-free hemolysates, the stroma of all individuals contained an excess of labeled .beta.-chains relative to .alpha.-chains after short incubation times. In Hb AA and AS individuals, the stromal .beta.A radioactivity was 1-2% of the total cellular .beta.A radioactivity. In Hb AS and SS individuals, the stromal .beta.S radioactivity was 3-5% and 10-20% of the total cellular .beta.S radioactivity, respectively. All of the stroma .beta.-chain radioactivity was associated with completed Hb molecules. Because of the unlabeled free .alpha.-chain pool found in reticulocytes, after short incubation times newly completed Hb molecules have predominantly labeled .beta.-chains and unlabeled .alpha.-chains. These findings suggest that part of the discrepancy between the stroma and stroma-free hemolysate .alpha./.beta. radioactivities seen in HbAS and HbSS individuals may result from normal labeling kinetics. A pulse chase experiment performed on an individual with HbSS revealed that completed HbS molecules, in addition to being associated with the stroma, were lost from the cell.