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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3544-3551.
Prepublished online as a Blood First Edition Paper on December 7, 2006; DOI 10.1182/blood-2006-07-035139.


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RED CELLS

Endothelial Lu/BCAM glycoproteins are novel ligands for red blood cell {alpha}4ß1integrin: role in adhesion of sickle red blood cells to endothelial cells

Wassim El Nemer1,3, Marie-Paule Wautier1,3, Cécile Rahuel1,3, Pierre Gane1,3, Patricia Hermand1,3, Frédéric Galactéros4, Jean-Luc Wautier2,3, Jean-Pierre Cartron1,3, Yves Colin1,3, and Caroline Le Van Kim1,3

1 Institut National de la Santé et de la Recherche Médicale (INSERM) U665, Paris, France; 2 Institut National de la Transfusion Sanguine, Paris, France; 3 University Paris 7, France; 4 Hôpital Henri Mondor, Assistance Publique Hôpitaux Paris (APHP), Créteil, France

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}4ß1, the unique integrin expressed on immature circulating sickle red cells. Using cell adhesion assays under static and flow conditions, we demonstrated that integrin {alpha}4ß1 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}4ß1 under flow conditions. Antibody-mediated activation of integrin {alpha}4ß1 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}4ß1 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.


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