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Decrease of very late activation antigen-4 and CD36 on reticulocytes in
sickle cell patients treated with hydroxyurea
LA Styles, B Lubin, E Vichinsky, S Lawrence, M Hua, S Test and F Kuypers
Department of Hematology/Oncology, Children's Hospital, Oakland, CA 94609,
USA.
Sickle cell disease (SCD) is characterized by repeated vaso-occlusive
events, which result in substantial morbidity. Abnormal adhesion of sickle
red blood cells (RBC) to the vascular endothelium is postulated to play a
role in the pathogenesis of vaso-occlusion. Two adhesion receptors, very
late activation antigen-4 (VLA-4) and CD36, are found in unusually high
numbers on sickle cell reticulocytes and do mediate adhesion of sickle RBC
to endothelium. Hydroxyurea (HU) therapy results in fewer vaso-occlusive
episodes, and we postulated that HU-related modulation of VLA-4 and CD36
receptors may contribute to its clinical benefit. Using flow cytometry,
eight patients were followed from the onset of HU treatment through a mean
treatment length of 200 +/- 49 days. Mean corpuscular volume and percent
fetal hemoglobin (Hb F) increased from 87% +/- 6% to 98% +/- 9% and 6.6%
+/- 3.9% to 12.7% +/- 5.6%, respectively. The percentage of reticulocytes
expressing VLA-4 decreased from 29.0% +/- 5.9% to 14.9% +/- 2.3% (P =
.0003). Two thirds of the total decrease in VLA-4 expression occurred after
10 weeks of HU and plateaued by 20 weeks. Changes in VLA-4 expression
occurred before substantial increases in Hb F. The percentage of
reticulocytes expressing CD36 decreased from 55.3% +/- 6.4% to 42.6% (P =
.0046). Changes in adhesion receptor expression were not caused by a
decrease in reticulocytosis with HU therapy. This report is the first to
associate a decrease in adhesion receptor expression with a therapy known
to reduce the clinical severity of SCD.
Volume 89,
Issue 7,
pp. 2554-2559,
04/01/1997
Copyright © 1997 by The American Society of Hematology
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