Odièvre Marie-Hélène, Bony Viviane, Benkerrou Malika, Lapouméroulie Claudine, Alberti Corinne, Ducrocq Rolande, Jacqz-Aigrain Evelyne, Elion Jacques, Cartron Jean-Pierre
INSERM, U763, Paris.
Haematologica. 2008 Apr;93(4):502-10. doi: 10.3324/haematol.12070. Epub 2008 Mar 5.
We investigated adhesion receptor levels on red blood cells, reticulocytes and erythroid progenitors from children with sickle cell disease treated or not with hydroxyurea.
Four groups of patients were investigated: (i) children receiving hydroxyurea for severe vaso-occlusive events (n=26); (ii) untreated children with a history of vaso-occlusive events (n=20); (iii) children with no history of vaso-occlusive events (n=28); and (iv) healthy African controls (n=27). Expression of adhesion receptors was analyzed by flow cytometry with specific mono-clonal antibodies.
Reticulocytes and/or red blood cells from the children with sickle cell disease showed significantly higher expression of CD36, alpha 4beta 1, Lu/BCAM than those from controls, whatever the severity of the disease, as well as less marked increases in expression of ICAM-4, CD47 and CD147. Under hydroxyurea treatment, the expression of CD36, alpha 4beta 1 and ICAM-4 (to a lesser extent) was decreased, but surprisingly the expression of Lu/BCAM (and also CD47 and CD147 to a lesser extent) was significantly increased. Alterations of levels of adhesion receptors could be recapitulated in two-phase liquid cultures of erythroid progenitors from controls and untreated children with a history of vaso-occlusive disease, grown in the absence or presence of hydroxyurea.
Our results suggest that hydroxyurea acts during erythroid development and modulates adhesion receptor expression and function differently, possibly by acting on gene expression and the signaling cascade leading to receptor activation.
我们研究了接受或未接受羟基脲治疗的镰状细胞病患儿红细胞、网织红细胞和红系祖细胞上黏附受体的水平。
对四组患者进行了研究：（i）因严重血管闭塞事件接受羟基脲治疗的儿童（n = 26）；（ii）有血管闭塞事件病史的未治疗儿童（n = 20）；（iii）无血管闭塞事件病史的儿童（n = 28）；以及（iv）健康非洲对照（n = 27）。使用特异性单克隆抗体通过流式细胞术分析黏附受体的表达。
无论疾病严重程度如何，镰状细胞病患儿的网织红细胞和/或红细胞显示出比对照组更高的CD36、α4β1、Lu/BCAM表达，以及ICAM - 4、CD47和CD147表达的增加幅度较小。在羟基脲治疗下，CD36、α4β1和ICAM - 4（程度较轻）的表达降低，但令人惊讶的是，Lu/BCAM（以及程度较轻的CD47和CD147）的表达显著增加。在有无羟基脲的情况下培养的对照组和有血管闭塞疾病病史的未治疗儿童的红系祖细胞的两相液体培养中，可以重现黏附受体水平的变化。
我们的结果表明，羟基脲在红系发育过程中起作用，并且可能通过作用于基因表达和导致受体激活的信号级联反应，以不同方式调节黏附受体的表达和功能。
