title: P-selectin glycoprotein ligand 1 and beta2-integrins cooperate in the adhesion of leukocytes to von Willebrand factor.
abstract: 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 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 beta2-integrin function. In addition, the isolated I-domain of alphaMbeta2 bound to VWF, and cell lines expressing alphaLbeta2 or alphaXbeta2 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 (beta2-integrins) adhesion. VWF is unique in its intrinsic capacity to combine the rolling and the stable adhesion step in the interaction with leukocytes.
authors.affiliation: INSERM U. 770, 80 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Pendu
authors.forename: Virginie
authors.initials: V
authors.lastname: Terraube
authors.forename: Olivier D
authors.initials: OD
authors.lastname: Christophe
authors.forename: Carl G
authors.initials: CG
authors.lastname: Gahmberg
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lenting
authors.forename: Cecile V
authors.initials: CV
authors.lastname: Denis
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D036904:Leukocyte Rolling / Q000187:drug effects / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020298:U937 Cells; D014842:von Willebrand Diseases / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D018821:CD18 Antigens; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D011994:Recombinant Proteins; D014841:von Willebrand Factor