title: Endothelial Lu/BCAM glycoproteins are novel ligands for red blood cell alpha4beta1 integrin: role in adhesion of sickle red blood cells to endothelial cells.
abstract: The Lutheran (Lu) blood group and basal cell adhesion molecule (BCAM) antigens are both carried by 2 glycoprotein isoforms of the immunoglobulin superfamily representing receptors for the laminin alpha(5) chain. In addition to red blood cells, Lu/BCAM proteins are highly expressed in endothelial cells. Abnormal adhesion of red blood cells to the endothelium could potentially contribute to the vaso-occlusive episodes in sickle cell disease. Considering the presence of integrin consensus-binding sites in Lu/BCAM proteins, we investigated their potential interaction with integrin alpha(4)beta(1), the unique integrin expressed on immature circulating sickle red cells. Using cell adhesion assays under static and flow conditions, we demonstrated that integrin alpha(4)beta(1) expressed on transfected cells bound to chimeric Lu-Fc protein. We showed that epinephrine-stimulated sickle cells, but not control red cells, adhered to Lu-Fc via integrin alpha(4)beta(1) under flow conditions. Antibody-mediated activation of integrin alpha(4)beta(1) induced adhesion of sickle red cells to primary human umbilical vein endothelial cells; this adhesion was inhibited by soluble Lu-Fc and vascular cell adhesion molecule-1 (VCAM-1)-Fc proteins. This novel interaction between integrin alpha(4)beta(1) in sickle red cells and endothelial Lu/BCAM proteins could participate in sickle cell adhesion to endothelium and potentially play a role in vaso-occlusive episodes.
authors.affiliation: INSERM Unité 665, Paris, France.
authors.forename: Wassim
authors.initials: W
authors.lastname: El Nemer
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Wautier
authors.forename: Cécile
authors.initials: C
authors.lastname: Rahuel
authors.forename: Pierre
authors.initials: P
authors.lastname: Gane
authors.forename: Patricia
authors.initials: P
authors.lastname: Hermand
authors.forename: Frédéric
authors.initials: F
authors.lastname: Galactéros
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Wautier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cartron
authors.forename: Yves
authors.initials: Y
authors.lastname: Colin
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Van Kim
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications / Q000378:metabolism*; D001157:Arterial Occlusive Diseases / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004913:Erythrocytes, Abnormal / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D008024:Ligands; D008188:Lutheran Blood-Group System / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism
chemical_list: D039041:Integrin alpha4beta1; D008024:Ligands; D008188:Lutheran Blood-Group System; D020033:Protein Isoforms