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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 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 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 Reheman, A. Articles by Ni, H. Search for Related Content PubMed PubMed Citation Articles by Reheman, A. Articles by Ni, H. Related Collections Platelets and Thrombopoiesis Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Plasma fibronectin depletion enhances platelet aggregation and thrombus formation in mice lacking fibrinogen and von Willebrand factor Adili Reheman1,2, Hong Yang13, Guangheng Zhu2, Wuxun Jin2, Feng He2, Christopher M. Spring2, Xufang Bai2,4, Peter L. Gross2,4, John Freedman1,2,5, and Heyu Ni13,5,6 1 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON; 2 Toronto Platelet Immunobiology Group and Department of Laboratory Medicine, Keenan Research Centre, Li Ka-Shing Knowledge Institute, St Michael's Hospital, Toronto, ON; 3 Canadian Blood Services, Toronto, ON; 4 Department of Medicine, The Henderson Research Centre, McMaster University, Hamilton, ON; and Departments of 5 Medicine and 6 Physiology, University of Toronto, Toronto, ON We previously showed 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), whereas 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 β3 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 showed 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 probably 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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