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Rapid increase in red blood cell density driven by K:Cl cotransport in a
subset of sickle cell anemia reticulocytes and discocytes
ME Fabry, JR Romero, ID Buchanan, SM Suzuka, G Stamatoyannopoulos, RL Nagel and M Canessa
Division of Hematology, Albert Einstein College of Medicine, Bronx, NY
10461.
We have previously demonstrated that young normal (AA) and sickle cell
anemia (SS) red blood cells are capable of a volume regulatory decrease
response (VRD) driven by a K:Cl cotransporter that is activated by low pH
or hypotonic conditions. We now report on the characteristics of young SS
cells (SS2, discocytes) capable of rapid increase in density in response to
swelling. We have isolated cells with high VRD response (H-VRD) and low VRD
response (L-VRD) cells by incubation and density- gradient centrifugation
under hypotonic conditions. Comparison of these cells in patients
homozygous for hemoglobin (Hb)S indicated that H-VRD cells have 91% more
reticulocytes (P less than 9 x 10(-9) than L-VRD cells, 25% less HbF (P
less than 5.5 x 10(-5), 106% more NEM (N- methylmaleimide)-stimulated K:Cl
cotransport activity (P less than 2 x 10(-4), and 86% more
volume-stimulated K:Cl cotransport activity (P less than 1.8 x 10(-3).
H-VRD and L-VRD cells have similar G-6-PD and Na+/H+ antiport activity. In
agreement with the reduced percent HbF in H-VRD cells, F cells (red blood
cells that contain fetal Hb) are depleted from the H-VRD population;
however, F reticulocytes are enriched in the H-VRD population to the same
extent as non-F reticulocytes, which suggests that both F and non-F
reticulocytes have a similar initial distribution of volume-sensitive K:Cl
cotransport activity but that it may be more rapidly inactivated in F than
in S reticulocytes. We find that H-VRD cells consist of 20% reticulocytes
(or 79% of all reticulocytes in SS2) and 80% more mature cells. This study
demonstrates the role of K:Cl cotransport in determining red blood cell
density, the heterogeneity of K:Cl cotransport activity in reticulocytes,
and the capacity for rapid change in the density of reticulocytes with high
K:Cl cotransport activity. We speculate that the H-VRD population may be
more susceptible to generation of dense and irreversibly sickled cells.
Volume 78,
Issue 1,
pp. 217-225,
07/01/1991
Copyright © 1991 by The American Society of Hematology
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