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Blood, 19 February 2009, Vol. 113, No. 8, pp. 1809-1817. Prepublished online as a Blood First Edition Paper on November 25, 2008; DOI 10.1182/blood-2008-04-148361. This Article Full Text (PDF) All Versions of this Article: blood-2008-04-148361v1 113/8/1809    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 Reheman, A. Articles by Ni, H. Search for Related Content PubMed PubMed Citation Articles by Reheman, A. Articles by Ni, H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 1, 2008 Accepted November 4, 2008 Plasma fibronectin depletion enhances platelet aggregation and thrombus formation in mice lacking fibrinogen and von Willebrand factor Adili Reheman, Hong Yang, Guangheng Zhu, Wuxun Jin, Feng He, Christopher M. Spring, Xufang Bai, Peter L. Gross, John Freedman, and Heyu Ni* Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada Canadian Blood Services, Toronto, Ontario, Canada Toronto Platelet Immunobiology Group and Department of Laboratory Medicine, Keenan Research Centre, Li Ka-Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada Department of Medicine, The Henderson Research Centre, McMaster University, Hamilton, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada Deptartment of Physiology, University of Toronto, Toronto, Ontario, Canada * Corresponding author; email: nih{at}smh.toronto.on.ca. We previously demonstrated that platelet aggregation and thrombus formation occurred in mice lacking both fibrinogen (Fg) and von Willebrand factor (VWF), and that plasma fibronectin (pFn) promoted thrombus growth and stability in injured arterioles in wild-type mice. To examine whether pFn is required for Fg/VWF-independent thrombosis, we generated Fg/VWF/conditional pFn triple deficient(TKO; Cre+, Fnflox/flox, Fg/VWF-/-) mice and littermate control (Cre-, Fnflox/flox, Fg/VWF-/-) mice. Surprisingly, TKO platelet aggregation was not abolished, but instead was enhanced in both heparinized platelet-rich plasma and gel-filtered platelets. This enhancement was diminished when TKO platelets were aggregated in pFn positive control platelet-poor plasma (PPP), while aggregation was enhanced when control platelets were aggregated in pFn depleted TKO PPP. The TKO platelet aggregation can be completely inhibited by our newly developed mouse anti-mouse 3 integrin antibodies but was not affected by anti-mouse GPIb antibodies. Enhanced platelet aggregation was also observed when heparinized TKO blood was perfused in collagen-coated perfusion chambers. Using intravital microscopy, we further demonstrated that thrombogenesis in TKO mice was enhanced in both FeCl3-injured mesenteric arterioles and laser-injured cremaster arterioles. Our data indicate that pFn is not essential for Fg/VWF-independent thrombosis and that soluble pFn is likely an important inhibitory factor for platelet aggregation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. J. Graham, Q. Ren, J. R. Dilks, P. Blair, S. W. Whiteheart, and R. Flaumenhaft Endobrevin/VAMP-8-dependent dense granule release mediates thrombus formation in vivo Blood, July 30, 2009; 114(5): 1083 - 1090. [Abstract] [Full Text] [PDF] H. Yang, S. Lang, Z. Zhai, L. Li, W. H. A. Kahr, P. Chen, J. Brkic, C. M. Spring, M. J. Flick, J. L. Degen, et al. Fibrinogen is required for maintenance of platelet intracellular and cell-surface P-selectin expression Blood, July 9, 2009; 114(2): 425 - 436. [Abstract] [Full Text] [PDF]

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