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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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Submitted July 12, 2006
Accepted November 30, 2006
Endothelial Lu/BCAM glycoproteins are novel ligands for red blood cell 4 1 integrin: role in adhesion of sickle red blood cells to endothelial cells
Wassim El Nemer, Marie-Paule Wautier, Cecile Rahuel, Pierre Gane, Patricia Hermand, Frederic Galacteros, Jean-Luc Wautier, Jean-Pierre Cartron, Yves Colin, and Caroline Le Van Kim*
INSERM, Paris, France
Institute National de la Transfusion Sanguine, Paris, France
University Paris, Paris, France
Hopital Henri Mondor, APHP, Creteil, France
* Corresponding author; email: levankim{at}idf.inserm.fr.
Lutheran (Lu) blood group and Basal Cell Adhesion Molecule (BCAM) antigens are both carried by two glycoprotein isoforms of the immunoglobulin superfamily representing receptors for laminin 5 chain. In addition to red blood cells, Lu/BCAM are highly expressed in endothelial cells. Abnormal adhesion of red blood cells to 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 4 1, the unique integrin expressed on immature circulating sickle red cells. Using cell adhesion assays under static and flow conditions, we demonstrated that integrin 4 1 expressed on transfected cells bound to chimeric Lu-Fc protein. We showed that epinephrine-stimulated sickle but not control red cells adhered to Lu-Fc via integrin 4 1 under flow conditions. Antibody mediated activation of integrin 4 1 induced adhesion of sickle red cells to primary human umbilical vein endothelial cells and this adhesion was inhibited by soluble Lu-Fc and VCAM-1-Fc proteins. This novel interaction between integrin 4 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.

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