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

Author:

Pendu Ronan1,Terraube Virginie1,Christophe Olivier D.1,Gahmberg Carl G.1,de Groot Philip G.1,Lenting Peter J.1,Denis Cecile V.1

Affiliation:

1. From the Laboratory for Thrombosis and Haemostasis, Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, The Netherlands; Institut National de la Santé el de la Recherche Médicale (INSERM) U770, Le Kremlin-Bicêtre, France; Faculté de Médecine Paris-Sud, Université Paris-Sud 11, Le Kremlin-Bicêtre, France; and Department of Biological and Environmental Sciences, University of Helsinki, Finland.

Abstract

AbstractVon 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 P-selectin glycoprotein ligand-1 (PSGL-1). Moreover, 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 were strongly inhibited (greater than 75%) by neutrophil-inhibitory factor, an inhibitor of β2-integrin function. In addition, the isolated I-domain of αMβ2 bound to VWF, and cell lines expressing αLβ2 or αXβ2 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 (β2-integrins) adhesion. VWF is unique in its intrinsic capacity to combine the rolling and the stable adhesion step in the interaction with leukocytes.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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