Styles L A, Lubin B, Vichinsky E, Lawrence S, Hua M, Test S, Kuypers F
Department of Hematology/Oncology, Children's Hospital, Oakland, CA 94609, USA.
Blood. 1997 Apr 1;89(7):2554-9.
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.
镰状细胞病（SCD）的特征是反复发生血管阻塞事件，这会导致严重的发病率。镰状红细胞（RBC）与血管内皮的异常粘附被认为在血管阻塞的发病机制中起作用。在镰状细胞网织红细胞中发现两种粘附受体，即极迟活化抗原-4（VLA-4）和CD36，其数量异常高，并且确实介导镰状RBC与内皮的粘附。羟基脲（HU）治疗可减少血管阻塞发作次数，我们推测HU对VLA-4和CD36受体的相关调节可能有助于其临床益处。使用流式细胞术，对8名患者从HU治疗开始进行随访，平均治疗时长为200±49天。平均红细胞体积和胎儿血红蛋白（Hb F）百分比分别从87%±6%增加到98%±9%，以及从6.6%±3.9%增加到12.7%±5.6%。表达VLA-4的网织红细胞百分比从29.0%±5.9%降至14.9%±2.3%（P = 0.0003）。VLA-4表达的总下降中有三分之二发生在HU治疗10周后，并在20周时趋于平稳。VLA-4表达的变化发生在Hb F大幅增加之前。表达CD36的网织红细胞百分比从55.3%±6.4%降至42.6%（P = 0.0046）。粘附受体表达的变化不是由HU治疗导致的网织红细胞增多减少引起的。本报告首次将粘附受体表达的降低与已知可减轻SCD临床严重程度的治疗方法联系起来。
