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Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-03-0850. This Article Full Text (PDF) Supplemental Video All Versions of this Article: 2003-03-0850v1 102/10/3609    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 Ni, H. Articles by Wagner, D. D Search for Related Content PubMed PubMed Citation Articles by Ni, H. Articles by Wagner, D. D Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted March 20, 2003 Accepted July 3, 2003 Control of thrombus embolization and fibronectin internalization by integrin IIb3 engagement of the fibrinogen chain Heyu Ni*, Jessie M Papalia, Jay L Degen, and Denisa D Wagner The Center for Blood Research, Boston, MA, USA; Department of Pathology, Harvard Medical School, Boston, MA, USA Children's Hospital Research Foundation, University of Cincinnati, Cincinnati, OH, USA * Corresponding author; email: nih{at}smh.toronto.on.ca. Fibrin(ogen) deficiency (Fg-/-) was shown previously to be compatible with rapid thrombus growth within injured arterioles, but platelet fibronectin content was increased and newly formed thrombi were unstable. To further define the role of fibrin(ogen) in thrombus formation and stabilization, platelet biology was examined in mice expressing a form of fibrinogen that clots normally but lacks the chain C-terminal binding site for IIb3 (Fg5). Thrombus growth within the arterioles of Fg5 mice appeared faster than in wild-type mice despite a far greater emboli formation. Unlike Fg-/- mice, the emboli were relatively small and released from the top of thrombi, rather than by fracture at the vessel wall. The fibronectin content in Fg5 platelets was also dramatically increased through a 3 integrin-dependent mechanism. It is concluded that: 1) Fibrin formation contributes to, but is not sufficient for, the stabilization of arterial thrombi. Platelet receptor engagement of the C-terminal of the Fg chain contributes to the stable incorporation of platelets into thrombi; 2) Alternative ligands to fibrinogen can support efficient thrombus growth; and 3) Fibrinogen is internalized through IIb3 engagement of the fibrinogen chain element and this interaction secondarily controls the fibronectin content of platelets. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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