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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1333-1341. Prepublished online as a Blood First Edition Paper on October 16, 2003; DOI 10.1182/blood-2003-03-0889. This Article Full Text (PDF) All Versions of this Article: 2003-03-0889v1 103/4/1333    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 Siljander, P. R-M Articles by Heemskerk, J. W M Search for Related Content PubMed PubMed Citation Articles by Siljander, P. R-M Articles by Heemskerk, J. W M Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted March 25, 2003 Accepted October 8, 2003 Platelet receptor interplay regulates collagen-induced thrombus formation in flowing human blood Pia R-M Siljander*, Imke C A Munnix, Peter A Smethurst, Hans Deckmyn, Theo Lindhout, Willem H Ouwehand, Richard W Farndale, and Johan W M Heemskerk Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom Departments of Biochemistry and Human Biology, CARIM, University of Maastricht, Maastricht, The Netherlands Laboratory for Thrombosis Research, KU Leuven, Kortrijk, Belgium Department of Hematology and National Blood Service, University of Cambridge, Cambridge, United Kingdom * Corresponding author; email: prms2{at}mole.bio.cam.ac.uk. The platelet glycoproteins (GP) Ib, integrin 21 and GPVI are considered central to thrombus formation. Recently, their relative importance has been re-evaluated based on data from murine knock-out models. To examine their relationship during human thrombus formation on collagen type I fibres at high shear (1000s-1), we tested a novel antibody against GPVI, an immunoglobulin single chain variable fragment, 10B12, together with specific antagonists for GPIb (12G1 Fab2) and 21 (6F1 mAb or GFOGER-GPP peptide). GPVI was found to be crucial for aggregate formation, Ca2+ signalling and phosphatidylserine (PS) exposure, but not primary adhesion, even with >97% receptor blockade. Inhibition of 21 revealed its involvement in Ca2+ signalling, PS exposure and aggregate size. Both GPIb and 21 contributed to primary adhesion, showing overlapping function. Co-inhibiting receptors revealed synergism in thrombus formation: co-inhibition of ADP receptors with collagen receptors further decreased adhesion and aggregation, and crucially, complete eradication of thrombus formation required co-inhibition of GPVI with either GPIb or 21. In summary, human platelet deposition on collagen depends on the concerted interplay of several receptors: GPIb in synergy with 21 mediating primary adhesion, reinforced by activation through GPVI, which further regulates the thrombus formation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Platelet collagen receptors play molecular ping-pong Mark L. Kahn Blood 2004 103: 1180-1181. [Full Text] [PDF] This article has been cited by other articles: K. Gilio, I. C. A. Munnix, P. Mangin, J. M. E. M. Cosemans, M. A. H. Feijge, P. E. J. van der Meijden, S. Olieslagers, M. B. Chrzanowska-Wodnicka, R. Lillian, S. Schoenwaelder, et al. Non-redundant Roles of Phosphoinositide 3-Kinase Isoforms {alpha} and {beta} in Glycoprotein VI-induced Platelet Signaling and Thrombus Formation J. Biol. Chem., December 4, 2009; 284(49): 33750 - 33762. [Abstract] [Full Text] [PDF] M. Mazzucato, M. R. Cozzi, M. Battiston, M. 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