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 Blood, 1 August 2007, Vol. 110, No. 3, pp. 894-901.
Prepublished online as a Blood First Edition Paper on April 5, 2007; DOI 10.1182/blood-2006-10-048298.

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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Increased adhesion to endothelial cells of erythrocytes from patients with polycythemia vera is mediated by laminin {alpha}5 chain and Lu/BCAM

Marie-Paule Wautier1, Wassim El Nemer1, Pierre Gane1, Jean-Didier Rain3, Jean-Pierre Cartron1,2, Yves Colin1, Caroline Le Van Kim1, and Jean-Luc Wautier2,3

1 Institut National de la Santé et de la Recherche Médicale (INSERM), U665; 2 Institut National de la Transfusion Sanguine; 3 Université Paris7/Denis Diderot, Unite de Formation et de Recherche (UFR) Médecine, Paris, France

Patients with polycythemia vera (PV) have a JAK2 (a cytosolic tyrosine kinase) mutation and an increased risk of vascular thrombosis related to red blood cell (RBC) mass and platelet activation. We investigated functional RBC abnormalities that could be involved in thrombosis. RBC adhesion to human umbilical vein endothelial cells (HUVECs) was measured by a radiometric technique and in a flow system by video microscopy, and adhesion molecule expression was determined using specific antibodies (against CD36, CD49d, ICAM-4, Lu/BCAM, CD147, and CD47) and flow cytometry in a group of 38 patients with PV and a group of 36 healthy volunteers. Adhesion of PV RBCs was 3.7-fold higher than that of normal RBCs (P < .001). Adhesion was inhibited when PV RBCs were incubated with anti-Lutheran blood group/basal cell adhesion molecule (Lu/BCAM) or when HUVECs were treated with anti-laminin {alpha}5 and to a lesser extent with anti-{alpha}3 integrin. Lu/BCAM was constitutively phosphorylated in PV RBCs. Transfection of K562 cells with JAK2 617V>F resulted in increased expression and phosphorylation of Lu/BCAM. Phosphorylation of Lu/BCAM increases RBC adhesion. Our results indicate that JAK2 mutation might be linked to Lu/BCAM modification and increased RBC adhesiveness, which may be a factor favoring thrombosis in PV.


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