P-selectin glycoprotein ligand 1 and β2-integrins cooperate in the adhesion of leukocytes to von Willebrand factor

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 was able to interact with polymorphonuclear leukocytes (PMNs) and monocytes under static and flow conditions. Adhesion under flow was dominated by short-lasting contact with resting PMNs, whereas adhesion of phorbol-12-myristate-13-acetate (PMA)stimulated PMNs was characterized by firm adhesion. Transient binding of PMNs to VWF appeared to be mediated by beta-selectin glycoprotein ligand-1 (PSGL-1). Moreover, recombinant PSGL-1 protein and cell surf ace-expressed PSGL-1 directly interacted with VWF. As for stable adhesion by PMA-stimulated PMNs, we observed that static adhesion and adhesion under flow were strongly inhibited (greater than 75%) by neutrophil-inhibitory factor, an inhibitor of beta 2-integrin function. In addition, the isolated I-domain of alpha M beta 2 bound to VWF, and cell lines expressing alpha L beta 2 or alpha X beta 2 adhered efficiently to VWF. Taken together, our data showed that VWF can function as an adhesive surface for various leukocyte subsets (monocytes, PMNs). Analogous to VWF-platelet interaction, VWF provided binding sites for leukocyte receptors involved in rolling (PSGL-1) and stable (beta 2-integrins) adhesion. VWF is unique in its intrinsic capacity to combine the rolling and the stable adhesion step in the interaction with leukocytes.