Phosphatidylserine (PS), exclusively present in the inner monolayer of the
normal red blood cell (RBC) membrane, is exposed in subpopulations of sickl
e cells. PS-exposing RBCs were found predominantly among the densest and th
e very light sickle cells. Within the light RBC fraction, PS exposure was f
ound on reticulocytes, transferrin receptor-expressing reticulocytes, and m
ature RBCs. The last subset contained low-density valinomycin-resistant RBC
s, previously shown to have high Na+ and low K+ content. This subpopulation
contained the highest percentage of PS-exposing cells. The PS-exposing sic
kle cells did not show the sustained high cytosolic Ca++ levels that have b
een shown to activate scramblase, activity. Data from this study indicate t
hat PS exposure can occur at different stages in the life of the sickle RBC
and that It correlates with the loss of aminophospholipid translocase acti
vity, the only common denominator of the PS-exposing cells. The additional
requirement of scramblase activation may occur during transient increases I
n cytosollc Ca++. (C) 2001 by The American Society of Hematology.