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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2461-2469. Prepublished online as a Blood First Edition Paper on November 9, 2006; DOI 10.1182/blood-2006-06-029082. This Article Full Text (PDF) All Versions of this Article: blood-2006-06-029082v1 109/6/2461    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 Evangelista, V. Articles by Smyth, S. S Search for Related Content PubMed PubMed Citation Articles by Evangelista, V. Articles by Smyth, S. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 13, 2006 Accepted October 30, 2006 Src family kinases mediate neutrophil adhesion to adherent platelets Virgilio Evangelista*, Zehra Pamuklar, Antonio Piccoli, Stefano Manarini, Giuseppe Dell'Elba, Romina Pecce, Nicola Martelli, Lorenzo Federico, Mauricio Rojas, Giorgio Berton, Clifford A Lowell, Licia Totani, and Susan S Smyth Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, Chieti, Italy Division of Cardiovascular Medicine, The Gill Heart Institute, The University of Kentucky, Lexington, KY, United States Carolina Cardiovascular Biology Center, The University of North Carolina, Durham, NC, United States Department of Pathology, University of Verona, Verona, Italy Department of Laboratory Medicine, University of California at San Francisco, San Francisco, CA, United States Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, Cheiti, Italy * Corresponding author; email: evangelista{at}negrisud.it. Polymorphonuclear leukocyte (PMN)-platelet interactions at sites of vascular damage contribute to local and systemic inflammation. We sought to determine the role of ''outside-in'' signaling by Src-family-kinases (SFK) in the regulation of M2 integrin-dependent PMN recruitment by activated platelets under (patho)physiologic conditions. Activation-dependent epitopes in integrin 2 were exposed at the contacts sites between PMNs and platelets and were abolished by SFK inhibitors. PMNs from M2-/-, hck-/-fgr-/- and hck-/-fgr-/-lyn-/- mice had an impaired capacity to adhere with activated platelets in suspension. Phosphorylation of Pyk2 accompanied PMN adhesion to platelets and was blocked by functional inhibition as well as by genetic deletion of M2 integrin and SFKs. A Pyk2 inhibitor reduced platelet-PMN adhesion, indicating that Pyk2 may be a down-stream effector of SFKs. Analysis of PMN-platelet interactions under flow revealed that SFK signaling was required for M2-mediated shear resistant adhesion of PMNs to adherent platelets, but was dispensable for P-selectin-PSGL-1-mediated recruitment and rolling. Finally, SFK activity was required to support PMN accumulation along adherent platelets at the site of vascular injury, in vivo. These results definitely establish a role for SFK in PMN recruitment by activated platelets and suggest novel targets to disrupt the pathophysiologic consequences of platelet-leukocyte interactions in vascular disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Maugeri, P. Rovere-Querini, V. Evangelista, C. Covino, A. Capobianco, M. T. S. Bertilaccio, A. Piccoli, L. Totani, D. Cianflone, A. Maseri, et al. Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and {beta}2 integrin-dependent cell clearance program Blood, May 21, 2009; 113(21): 5254 - 5265. [Abstract] [Full Text] [PDF] F. A. Bozza, A. M. Shah, A. S. Weyrich, and G. A. Zimmerman Amicus or Adversary: Platelets in Lung Biology, Acute Injury, and Inflammation Am. J. Respir. Cell Mol. Biol., February 1, 2009; 40(2): 123 - 134. [Abstract] [Full Text] [PDF] R. Paul, B. Obermaier, J. Van Ziffle, B. Angele, H.-W. Pfister, C. A. Lowell, and U. Koedel Myeloid Src kinases regulate phagocytosis and oxidative burst in pneumococcal meningitis by activating NADPH oxidase J. Leukoc. Biol., October 1, 2008; 84(4): 1141 - 1150. [Abstract] [Full Text] [PDF] R. Cheung, V. Ravyn, L. Wang, A. Ptasznik, and R. G. Collman Signaling Mechanism of HIV-1 gp120 and Virion-Induced IL-1{beta} Release in Primary Human Macrophages J. Immunol., May 15, 2008; 180(10): 6675 - 6684. [Abstract] [Full Text] [PDF] T. Tougan, H. Onda, D. Okuzaki, S. Kobayashi, H. Hashimoto, and H. Nojima Focused Microarray Analysis of Peripheral Mononuclear Blood Cells from Churg-Strauss Syndrome Patients DNA Res, April 1, 2008; 15(2): 103 - 114. [Abstract] [Full Text] [PDF] G. Li, J. M. Sanders, M. H. Bevard, Z. Sun, J. W. Chumley, E. V. Galkina, K. Ley, and I. J. Sarembock CD40 Ligand Promotes Mac-1 Expression, Leukocyte Recruitment, and Neointima Formation after Vascular Injury Am. J. Pathol., April 1, 2008; 172(4): 1141 - 1152. [Abstract] [Full Text] [PDF] H. Nakayama, F. Yoshizaki, A. Prinetti, S. Sonnino, L. Mauri, K. Takamori, H. Ogawa, and K. Iwabuchi Lyn-coupled LacCer-enriched lipid rafts are required for CD11b/CD18-mediated neutrophil phagocytosis of nonopsonized microorganisms J. Leukoc. Biol., March 1, 2008; 83(3): 728 - 741. [Abstract] [Full Text] [PDF] M. Choi, B. Salanova, S. Rolle, M. Wellner, W. Schneider, F. C. Luft, and R. Kettritz Short-Term Heat Exposure Inhibits Inflammation by Abrogating Recruitment of and Nuclear Factor-{kappa}B Activation in Neutrophils Exposed to Chemotactic Cytokines Am. J. Pathol., February 1, 2008; 172(2): 367 - 777. [Abstract] [Full Text] [PDF] G. Li, A. C. Keenan, J. C. Young, M. J. Hall, Z. Pamuklar, E. M. Ohman, S. R. Steinhubl, and S. S. Smyth Effects of Unfractionated Heparin and Glycoprotein IIb/IIIa Antagonists Versus Bivalirdin on Myeloperoxidase Release From Neutrophils Arterioscler Thromb Vasc Biol, August 1, 2007; 27(8): 1850 - 1856. [Abstract] [Full Text] [PDF]

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