General review Red cell and endothelial Lu/BCAM beyond sickle cell disease § Role des glycoproteines Lu/BCAM erythroõ ¨des et endotheliales en dehors de la drepanocytose

AbstractRecent studies shed new lights on the biological function of blood group antigens, such as the adhesion properties of the Lutheran (Lu) bloodgroup antigens carried by the Lu/BCAM glycoproteins. The Lu/BCAM adhesion glycoproteins were Þrst identiÞed as laminin-10/11 erythroidreceptors involved in RBC adhesion to endothelium in sickle cell anemia. Lu/BCAM mediated cell adhesion to laminin is stimulated byepinephrine, a physiological stress mediator, and is dependent of phosphorylation by protein kinase A. More recently, we demonstrated thatconstitutive phosphorylation of Lu/BCAM is also involved in abnormal RBC adhesion to endothelium in patients with polycythemia vera (PV), afrequent myeloproliferative disorders associated with the V617F mutation of the tyrosine kinase JAK2 leading to continuous stimulation oferythropoiesis. This observation suggests that Lu/BCAM could participate to the high incidence of vascular thrombosis that also characterizes PVdisease. In mice, which do not express Lu/BCAM in erytroid tissues, invalidation of theLu/BCAMgene provided evidence that Lu/BCAM gps, aslaminin-a5 receptors, are involved invivo in the maintenance of normal basement membrane organization in different non erythroid tissues sinceup to 90% of the mutant kidney glomeruli exhibited a reduced number of visible capillary lumens and irregular thickening of the glomerularbasement membrane, while intestine exhibited smooth muscle coat thickening and disorganization. All these results further illustrate that minorblood group antigens might have important role under physiological and physiopathological conditions in erythroid and non erythroid tissues aswell.# 2008 Elsevier Masson SAS. All rights reserved.ResumeDes Žtudes rŽcentes ont apportŽ de nouvelles informations sur la fonction des antignes de groupes sanguins, telles que les propriŽtŽsdOadhŽrence des antignes LuthŽran (Lu) portŽs par les glycoprotŽines Lu/BCAM. Ces glycoprotŽines ont dOabord ŽtŽ identiގes comme lesuniques rŽcepteurs Žrythro•des des laminines-10/11 (composants majeurs de la matrice extracellulaire) impliquŽs dans lOadhŽrence anormale desglobules rouges drŽpanocytaires ˆ lOendothŽlium vasculaire. Ces propriŽtŽs dOadhŽrence de Lu/BCAM sont stimulŽes par lOadrŽnaline, unmŽdiateur physiologique de stress induisant la phosphorylation de Lu/BCAM par la protŽine kinase A. Plus rŽcemment, nous avons dŽmontrŽ quela phosphorylation constitutive de Lu/BCAM est Žgalement impliquŽe dans lOadhŽrence anormale ˆ lOendothŽlium des globules rouges de patientsatteint de polyglobulie de Vaquez (polycythemia vera: PV), un dŽsordre myŽloprolifŽratif frŽquent associŽ ˆ la mutation V617F de la tyrosinekinase JAK2 et conduisant ˆ une stimulation continue de lOŽrythropo•se. Ainsi Lu/BCAM participerait ˆ lOincidence ŽlevŽe des Žvnementsthrombotiques qui caractŽrise Žgalement la polyglobulie de Vaquez. Chez la souris, qui nOexprime pas Lu/BCAM dans les cellules Žrythro•des,lOinactivation du gneLu/BCAMa permis de montrer que les protŽines Lu/BCAM, en tant que rŽcepteurs aux laminines-10/11, sont impliquŽesdans le maintien de lOorganisation des membranes basales de nombreux tissus. Ainsi jusquOˆ 90 % des glomŽrules rŽnaux des sourisLu/BCAM