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Blood, 15 November 2003, Vol. 102, No. 10, pp. 3637-3645. Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-02-0496. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-02-0496v1 102/10/3637    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Thai, L. M. Articles by Jackson, D. E. Search for Related Content PubMed PubMed Citation Articles by Thai, L. M. Articles by Jackson, D. E. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Physical proximity and functional interplay of PECAM-1 with the Fc receptor FcRIIa on the platelet plasma membrane Le M. Thai, Leonie K. Ashman, Stacey N. Harbour, P. Mark Hogarth, and Denise E. Jackson From the Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia; University of Newcastle, Callaghan, New South Wales, Australia. We and others have recently defined that Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1/CD31) functions as a negative regulator of platelet-collagen interactions involving the glycoprotein VI/Fc receptor gamma chain (GPVI/FcR- chain) signaling pathway.1,2 In this study, we hypothesized that PECAM-1 may be physically and functionally associated with FcRIIa on the platelet membrane. The functional relationship between PECAM-1 and FcRIIa was assessed by determining the effect of anti-PECAM-1 monoclonal antibody Fab fragments on FcRIIa-mediated platelet aggregation and heparin-induced thrombocytopenia (HITS)-mediated platelet aggregation. Preincubation of washed platelets with monoclonal antibody fragments of 2BD4 directed against PECAM-1 and IV.3 directed against FcRIIa completely blocked FcRIIa-mediated platelet aggregation and HITS-mediated platelet aggregation, whereas anti-CD151 antibody had no blocking effect. Coengagement of FcRIIa and PECAM-1 resulted in negative regulation of FcRIIa-mediated phospholipase C2 activation, calcium mobilization, and phosphoinositide 3-kinase-dependent signaling pathways. In addition, the physical proximity of FcRIIa and PECAM-1 was confirmed by using fluorescence resonance energy transfer and coimmunoprecipitation studies. These results indicate that PECAM-1 and FcRIIa are colocalized on the platelet membrane and PECAM-1 down-regulates FcRIIa-mediated platelet responses. (Blood. 2003;102:3637-3645) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Rivera, M. L. Lozano, L. Navarro-Nunez, and V. Vicente Platelet receptors and signaling in the dynamics of thrombus formation Haematologica, May 1, 2009; 94(5): 700 - 711. [Abstract] [Full Text] [PDF] R. K. Andrews, D. Karunakaran, E. E. Gardiner, and M. C. 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Platelet PECAM-1 inhibits thrombus formation in vivo Blood, January 15, 2006; 107(2): 535 - 541. [Abstract] [Full Text] [PDF] J. L. Wee and D. E. Jackson The Ig-ITIM superfamily member PECAM-1 regulates the "outside-in" signaling properties of integrin {alpha}IIb{beta}3 in platelets Blood, December 1, 2005; 106(12): 3816 - 3823. [Abstract] [Full Text] [PDF] L.-M. Lau, J. L. Wee, M. D. Wright, G. W. Moseley, P. M. Hogarth, L. K. Ashman, and D. E. Jackson The tetraspanin superfamily member CD151 regulates outside-in integrin {alpha}IIb{beta}3 signaling and platelet function Blood, October 15, 2004; 104(8): 2368 - 2375. [Abstract] [Full Text] [PDF] S. M. Albelda, K. C. Lau, P. Chien, Z.-Y. Huang, E. Arguiris, A. Bohen, J. Sun, J. A. Billet, M. Christofidou-Solomidou, Z. K. Indik, et al. Role for Platelet-Endothelial Cell Adhesion Molecule-1 in Macrophage Fc{gamma} Receptor Function Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2): 246 - 255. [Abstract] [Full Text] [PDF] J. M. 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