Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea.
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.
Styles
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LA
Department of Hematology/Oncology, Children's Hospital, Oakland, CA 94609, USA.
Lubin
B
B
Vichinsky
E
E
Lawrence
S
S
Hua
M
M
Test
S
S
Kuypers
F
F
D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy*; D000986:Antisickling Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018955:CD36 Antigens / Q000097:blood*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D004913:Erythrocytes, Abnormal / Q000737:chemistry* / Q000187:drug effects; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology / Q000627:therapeutic use*; D039041:Integrin alpha4beta1; D016023:Integrins / Q000097:blood; D008297:Male; D016201:Receptors, Lymphocyte Homing / Q000097:blood; D012156:Reticulocytes / Q000737:chemistry* / Q000187:drug effects
D000986:Antisickling Agents; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D006918:Hydroxyurea