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