Modulation of Erythrocyte Membrane Mechanical Stability by 2,3-Diphosphoglycerate in the Neonatal Poikilocytosis/Elliptocytosis Syndrome William C
Modulation of Erythrocyte Membrane Mechanical Stability by 2,3-Diphosphoglycerate in the Neonatal Poikilocytosis/Elliptocytosis Syndrome William C. Mentzer, Jr.,* Terri A. Iarocci,* Narla Mohandas,* Peter A. Lane,* Byron Smith,* Jack Lazerson,t and Taru Hays *Departments ofPediatrics and Laboratory Medicine, University ofCalifornia, San Francisco, California 94102; $The Department ofPediatrics, University ofCalifornia, Davis, California 95616; §Denver Children's Hospital and the Department ofPediatrics, University ofColorado School ofMedicine, Denver, Colorado 80220 Abstract fetal and adult red cells (7-9). We therefore considered it more likely that developmental changes in nonskeletal red cell com- To explain the transient anemia and poikilocytosis seen during ponents capable ofinteracting with the underlying skeletal pro- infancy in hereditary elliptocytosis (HE), we resealed erythrocyte tein abnormality were responsible for transient neonatal poi- (RBC) ghosts from affected children or their elliptocytic parents kilocytosis and hemolysis. In this report, we provide evidence with 2,-diphosphoglycerate (DPG) (0-8 mM), a compound that that 2,3-diphosphoglycerate (DPG)' can dissociate the flawed dissociates membrane skeletons, then measured ghost mechan- membrane skeleton of elliptocytic ghosts, causing such prepa- ical stability in the ektacytometer. Without added 2,3-DPG, rations to reach the extreme levels of mechanical fragility char- ghost mechanical stability was subnormal in infantile poikilo- acteristic of hereditary pyropoikilocyte ghosts. cytosis (IP) and HE but was even more abnormal in hereditary We propose that the uniquely high levels of free 2,3-DPG pyropoikilocytosis (HPP). Addition of 2,3-DPG (2.55 mM) to in fetal red cells, a consequence ofthe extremely limited ability IP or HE ghosts, decreased their stability to that of HPP ghosts ofhemoglobin F to bind 2,3-DPG, render cells with an inherited (without 2,3-DPG).
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