Improved solubility of deoxygenated hemoglobin in sickle cell disease: Correlations between erythrocytic Ca 2+ -ion concentration and hemoglobin solubility

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.