Erythrocyte membrane vesicles and irreversibly sickled cells bind protein S.
Plasma levels of free protein S, a vitamin K-dependent anticoagulant, are decreased in persons with sickle cell anemia, but the etiology of the low levels is unknown. Protein S binds to phosphatidylserine-containing phospholipids in a calcium-dependent manner. Other studies have indicated that phosphatidylserine may be abnormally present on the outer surface of the membrane lipid bilayer of sickle cells and of the spectrin-depleted vesicles they shed in vivo. We studied the binding of purified, radiolabeled protein S to spectrin-depleted erythrocyte membrane vesicles and to density-separated fractions of sickle and normal erythrocytes. Calcium-dependent binding of protein S occurred with vesicles and with well-aerated dense irreversibly sickled cells, but not with well-aerated sickle discocytes or with normal erythrocytes. These data provide further evidence that phosphatidylserine is abnormally present on the outer surface of spectrin-depleted vesicles and of irreversibly sickled cells. In addition, protein S binding to such sickle membranes in vivo may be responsible, in part, for the decreased levels of free protein S in sickle cell plasma.
Colorado Sickle Cell Treatment and Research Center, University of Colorado School of Medicine, Denver.
P A
PA
Lane
J L
JL
O'Connell
R A
RA
Marlar
D000755:Anemia, Sickle Cell / Q000097:blood*; D002118:Calcium / Q000378:metabolism; D002474:Cell-Free System; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004913:Erythrocytes, Abnormal / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D011485:Protein Binding; D017293:Protein S / Q000378:metabolism*; D011516:Prothrombin / Q000378:metabolism; D013049:Spectrin / Q000378:metabolism
D017293:Protein S; D013049:Spectrin; D011516:Prothrombin; D002118:Calcium