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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3746-3752. Prepublished online as a Blood First Edition Paper on August 22, 2006; DOI 10.1182/blood-2006-03-010322. This Article Full Text (PDF) Supplemental Videos All Versions of this Article: blood-2006-03-010322v1 108/12/3746    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pendu, R. Articles by Denis, C. V Search for Related Content PubMed PubMed Citation Articles by Pendu, R. Articles by Denis, C. V Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Sticky business: von Willebrand factor in inflammation José A. López Blood 2006 108: 3627. [Full Text] [PDF] This article has been cited by other articles: B.-Q. Zhao, A. K. Chauhan, M. Canault, I. S. Patten, J. J. Yang, M. Dockal, F. Scheiflinger, and D. D. Wagner von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke Blood, October 8, 2009; 114(15): 3329 - 3334. [Abstract] [Full Text] [PDF] D. M. Monson, J. R. Smith, M. L. Klein, and D. J. 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