Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea
Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea
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DOI：
10.1182/blood.v89.7.2554
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发表时间：
1997-04-01
期刊：
影响因子：
20.3
通讯作者：
Kuypers, F
中科院分区：
文献类型：
--
作者：
Styles, LA;Lubin, B;Kuypers, F
Sickle cell disease (SCD) is characterized by repeated vasoocclusive 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. (C) 1997 by The American Society of Hematology.
