Modulation of erythroid adhesion receptor expression by hydroxyurea in children with sickle cell disease.
BACKGROUND
We investigated adhesion receptor levels on red blood cells, reticulocytes and erythroid progenitors from children with sickle cell disease treated or not with hydroxyurea.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Odièvre
Marie-Hélène
MH
INSERM, U763, Paris.
Bony
Viviane
V
Benkerrou
Malika
M
Lapouméroulie
Claudine
C
Alberti
Corinne
C
Ducrocq
Rolande
R
Jacqz-Aigrain
Evelyne
E
Elion
Jacques
J
Cartron
Jean-Pierre
JP
D017954:Africa South of the Sahara / Q000208:ethnology; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001157:Arterial Occlusive Diseases / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D051926:Basigin / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D051928:CD47 Antigen / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000378:metabolism; D002648:Child; D004903:Erythrocyte Aggregation / Q000187:drug effects*; D004912:Erythrocytes / Q000737:chemistry; D015672:Erythroid Precursor Cells / Q000737:chemistry; D004920:Erythropoiesis / Q000187:drug effects; D005500:Follow-Up Studies; D005602:France; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology / Q000627:therapeutic use*; D039041:Integrin alpha4beta1 / Q000378:metabolism; D008188:Lutheran Blood-Group System; D008562:Membrane Glycoproteins / Q000097:blood*; D009363:Neoplasm Proteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000097:blood*; D012156:Reticulocytes / Q000737:chemistry; D063267:Sialic Acid Binding Ig-like Lectin 1; D015398:Signal Transduction / Q000187:drug effects
C090228:BCAM protein, human; C497886:BSG protein, human; D018955:CD36 Antigens; D051928:CD47 Antigen; C497894:CD47 protein, human; D015815:Cell Adhesion Molecules; C095100:ICAM4 protein, human; D039041:Integrin alpha4beta1; D008188:Lutheran Blood-Group System; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; D051926:Basigin; D006918:Hydroxyurea