Improved solubility of deoxygenated hemoglobin in sickle cell disease: Correlations between erythrocytic Ca2+-ion concentration and hemoglobin solubility
Affiliations: [a] Department of Pediatrics, University of Göttingen, FRG | [b] Max-Planck-Institute for Biophysical Chemistry, Göttingen, FRG | [c] Department of Pediatrics, Klinikum Minden, FRG
Note: [*] Present address: Dr. E. Friederichs, Department of Physiology and Biophysics, University of Southern California, School of Medicine, 1333 San Pablo Street, Los Angeles, CA 90033, U.S.A.
Note: [] Accepted by: Editor A.M. Ehrly
Abstract: Erythrocyte suspensions from eight patients suffering from sickle cell disease were incubated (1/2 h, 37°C) with pentoxifylline (10 µg/ml ≈ 40 µmol/l) or nifedipine (1 µg/ml ≈ 4 µmol/l), respectively. The “hemoglobin solubility” was taken as hemoglobin concentration in the supernatant after sedimentation of hemoglobin polymers from deoxygenated solutions by ultracentrifugation. Before and after incubation the concentrations of the intraerythrocytic Ca2+-ion and 2,3-diphosphoglycerate (2,3-DPG) were determined. Both, pentoxifylline and nifedipine, caused an increase in hemoglobin solubility of up to 30 % if the intracellular Ca2+-ion concentration was lowered from 0.38 ± 0.08 × 10−6 mol to nearly normal values (0.27 ± 0.10 × 10−6 mol). Concurrently the 2,3-DPG concentration decreased only slightly in both cases. A model is presented that accounts for intracellular Ca2+-ion concentration as a determining factor of the polymerization of hemoglobin leading to an altered deformability of the red cell.
