Submitted March 15, 2006
Accepted July 10, 2006
P-selectin glycoprotein 1 ligand (PSGL-1) and 
2-integrins cooperate in adhesion of leukocytes to von Willebrand factor
Ronan Pendu, Virginie Terraube, Olivier D Christophe, Carl G Gahmberg, Philip G de Groot, Peter J Lenting, and Cecile V Denis*
Laboratory for Thrombosis and Haemostasis, University Medical Center Utrecht, The Netherlands
INSERM, Le Kremlin-Bicetre, France
Department of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland
NSERM, Le Kremlin-Bicetre, France
* Corresponding author; email: denis{at}kb.inserm.fr.
Von Willebrand factor (VWF) is an essential component of hemostasis. However, animal studies using VWF-deficient mice suggest that VWF may also contribute to inflammation. In the present study, we demonstrate that VWF is able to interact with polymorphonuclear cells (PMNs) and monocytes under both static and flow conditions. Adhesion under flow is dominated by short-lasting contacts using resting PMNs, while adhesion of phorbol-12-myristate-13-acetate (PMA)-stimulated PMNs is characterized by firm adhesion. Transient binding of PMNs to VWF was found to be mediated by P-selectin glycoprotein ligand-1 (PSGL-1). Moreover, both recombinant PSGL-1 protein and cell-surface expressed PSGL-1 directly interacted with VWF. As for stable adhesion by PMA-stimulated PMNs, we observed that static adhesion and adhesion under flow was strongly inhibited (>75 %) by neutrophil-inhibitory factor, an inhibitor of 
2-integrin function. In addition, isolated I-domain of 
M2 bound to VWF, and cell-lines expressing L2 or X2 adhered efficiently to VWF. Taken together, our data show that VWF can function as an adhesive surface for various leukocyte subsets (monocytes, PMNs). In analogy with the VWF-platelet interaction, VWF provides binding sites for leukocyte-receptors involved in rolling (PSGL-1) and stable adhesion (2-integrins). To our knowledge, VWF is unique in its intrinsic capacity to combine both the rolling- and stable adhesion-step in the interaction with leukocytes.
