dc.contributor.author | Posner, MG | |
dc.contributor.author | Upadhyay, A | |
dc.contributor.author | Abubaker, AA | |
dc.contributor.author | Fortunato, TM | |
dc.contributor.author | Vara, D | |
dc.contributor.author | Canobbio, I | |
dc.contributor.author | Bagby, S | |
dc.contributor.author | Pula, G | |
dc.date.accessioned | 2018-01-10T08:59:26Z | |
dc.date.issued | 2016-02-05 | |
dc.description.abstract | Extracellular fibrinogen-binding protein (Efb) from Staphylococcus aureus inhibits platelet activation, although its mechanism of action has not been established. In this study, we discovered that the N-terminal region of Efb (Efb-N) promotes platelet binding of fibrinogen and that Efb-N binding to platelets proceeds via two independent mechanisms: fibrinogen-mediated and fibrinogen-independent. By proteomic analysis of Efb-interacting proteins within platelets and confirmation by pulldown assays followed by immunoblotting, we identified P-selectin and multimerin-1 as novel Efb interaction partners. The interaction of both P-selectin and multimerin-1 with Efb is independent of fibrinogen. We focused on Efb interaction with P-selectin. Excess of P-selectin extracellular domain significantly impaired Efb binding by activated platelets, suggesting that P-selectin is the main receptor for Efb on the surface of activated platelets. Efb-N interaction with P-selectin inhibited P-selectin binding to its physiological ligand, P-selectin glycoprotein ligand-1 (PSGL-1), both in cell lysates and in cell-free assays. Because of the importance of P-selectin-PSGL-1 binding in the interaction between platelets and leukocytes, we tested human whole blood and found that Efb abolishes the formation of platelet-monocyte and platelet-granulocyte complexes. In summary, we present evidence that in addition to its documented antithrombotic activity, Efb can play an immunoregulatory role via inhibition of P-selectin-PSGL-1-dependent formation of platelet-leukocyte complexes. | en_GB |
dc.description.sponsorship | This work was possible thanks to grants from Biotechnology and Biological Sciences Research Council (BBSRC) (BB/J002690/1 and BB/J008176/1), Wellcome Trust (ZR-W0258A), British Heart Foundation (PG/15/40/31522), and Royal Society Grant RG120494. T | en_GB |
dc.identifier.citation | Vol. 291 (6), pp. 2764 - 2776 | en_GB |
dc.identifier.doi | 10.1074/jbc.M115.678359 | |
dc.identifier.uri | http://hdl.handle.net/10871/30883 | |
dc.language.iso | en | en_GB |
dc.publisher | American Society for Biochemistry and Molecular Biology | en_GB |
dc.rights | © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Open access. Final version free via Creative Commons CC-BY license. | en_GB |
dc.subject | bacterial pathogenesis | en_GB |
dc.subject | fibrinogen | en_GB |
dc.subject | monocyte | en_GB |
dc.subject | neutrophil | en_GB |
dc.subject | platelet | en_GB |
dc.subject | proteomics | en_GB |
dc.subject | Staphylococcus aureus (S. aureus) | en_GB |
dc.subject | P-selectin | en_GB |
dc.subject | PSGL-1 | en_GB |
dc.subject | protein-protein interactions | en_GB |
dc.title | Extracellular Fibrinogen-binding Protein (Efb) from Staphylococcus aureus Inhibits the Formation of Platelet-Leukocyte Complexes | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-01-10T08:59:26Z | |
dc.identifier.issn | 0021-9258 | |
dc.description | This is the final version of the article. Available from American Society for Biochemistry and Molecular Biology via the DOI in this record. | en_GB |
dc.identifier.journal | Journal of Biological Chemistry | en_GB |