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Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea.
Blood. 1997 Apr 01; 89(7):2554-9.Blood

Abstract

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.

Authors+Show Affiliations

Department of Hematology/Oncology, Children's Hospital, Oakland, CA 94609, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9116302

Citation

Styles, L A., et al. "Decrease of Very Late Activation Antigen-4 and CD36 On Reticulocytes in Sickle Cell Patients Treated With Hydroxyurea." Blood, vol. 89, no. 7, 1997, pp. 2554-9.
Styles LA, Lubin B, Vichinsky E, et al. Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea. Blood. 1997;89(7):2554-9.
Styles, L. A., Lubin, B., Vichinsky, E., Lawrence, S., Hua, M., Test, S., & Kuypers, F. (1997). Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea. Blood, 89(7), 2554-9.
Styles LA, et al. Decrease of Very Late Activation Antigen-4 and CD36 On Reticulocytes in Sickle Cell Patients Treated With Hydroxyurea. Blood. 1997 Apr 1;89(7):2554-9. PubMed PMID: 9116302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea. AU - Styles,L A, AU - Lubin,B, AU - Vichinsky,E, AU - Lawrence,S, AU - Hua,M, AU - Test,S, AU - Kuypers,F, PY - 1997/4/1/pubmed PY - 1997/4/1/medline PY - 1997/4/1/entrez SP - 2554 EP - 9 JF - Blood JO - Blood VL - 89 IS - 7 N2 - 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. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/9116302/Decrease_of_very_late_activation_antigen_4_and_CD36_on_reticulocytes_in_sickle_cell_patients_treated_with_hydroxyurea_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)59066-6 DB - PRIME DP - Unbound Medicine ER -