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Hydroxyurea affects cell morphology, cation transport, and red blood cell
adhesion in cultured vascular endothelial cells
NC Adragna, P Fonseca and PK Lauf
Department of Pharmacology, Wright State University, School of Medicine,
Dayton, OH 45401-0927.
Hydroxyurea (HU) significantly increases fetal hemoglobin (Hb) production
and concomitantly affects passive erythrocyte K transport and cell volume
in patients homozygous for Hb S, thus decreasing disease severity. Red
blood cells (RBCs) with Hb S display a greater adherence to vascular
endothelial cells (VECs) than do Hb A cells, thus increasing the
probability of vaso-occlusive crisis. The effect of HU on the structure and
function of VECs is still unknown. In the present study, HU significantly
changed, in a dose-dependent manner, the morphology and monovalent cation
composition of cultured VECs after incubation in normal culture medium for
up to 10 days in the absence and presence of 0.3 (therapeutic dose) and 3.0
(toxic dose) mmol/L HU. Treated cells showed significant morphologic
changes such as an increase in apparent cell size and the formation of
multinucleated giant cells. The protein content per dish decreased by 50%
and 80% at 0.3 and 3.0 mmol/L HU, respectively, accompanied by an increase
in cell Na (maximum, approximately 200%) and cell K (maximum, approximately
50%) contents at about days 4 to 6 and 8 to 10, respectively. In addition,
HU decreased RBC adherence to VECs in experiments with 51Cr- loaded Hb A or
Hb S RBCs. The HU-induced changes in VEC morphology, cation composition,
and RBC adherence may be caused or accompanied by alterations in cell
membrane permeability, transformation of endothelial cells, or decreased
number/density of VEC adhesion molecules. Precise mechanisms of the HU
effects warrant further investigation in light of the reported beneficial
effects of HU in the treatment of sickle cell anemia.
Volume 83,
Issue 2,
pp. 553-560,
01/15/1994
Copyright © 1994 by The American Society of Hematology
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