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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1509-1514. Prepublished online as a Blood First Edition Paper on May 2, 2006; DOI 10.1182/blood-2005-11-011957. This Article Full Text (PDF) Supplemental Video All Versions of this Article: blood-2005-11-011957v1 108/5/1509    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 Larson, M. K Articles by Watson, S. P Search for Related Content PubMed PubMed Citation Articles by Larson, M. K Articles by Watson, S. P Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 25, 2005 Accepted April 16, 2006 Regulation of proplatelet formation and platelet release by integrin IIb3 Mark K Larson* and Steve P Watson Centre for Cardiovascular Sciences, Institute for Biomedical Research, University of Birmingham, UK * Corresponding author; email: m.larson{at}bham.ac.uk. Mature megakaryocytes form structures called proplatelets that serve as conduits for platelet packaging and release at vascular sinusoids. Since the megakaryocyte expresses abundant levels of integrin IIb3, we have examined a role for fibrinogen in proplatelet development and platelet release alongside that of other matrices. Primary mature murine megakaryocytes from bone marrow aspirates readily formed proplatelets when plated on fibrinogen at a degree that was significantly higher than seen on other matrices. Additionally, IIb3 was essential for proplatelet formation on fibrinogen, as megakaryocytes failed to develop proplatelets in the presence of IIb3 antagonists. Interestingly, inhibition of Src kinases or Ca2+ release did not inhibit proplatelet formation, indicating that IIb3-mediated outside-in signals are not required for this response. Immunohistochemical studies demonstrated that fibrinogen is localized to the bone marrow sinusoids, a location that would allow it to readily influence platelet release. Further, thrombopoietin-stimulated IIb-/- mice had a reduced increase in platelet number relative to controls. A similar observation was not observed for platelet recovery in IIb-/- mice in response to antibody- induced thrombocytopenia, indicating the existence of additional pathways of regulation of proplatelet formation. These results demonstrate that fibrinogen is able to regulate proplatelet formation via integrin IIb3. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Proplatelet formation: IIb or not IIb? Andrew D. Leavitt Blood 2006 108: 1429. [Full Text] [PDF] This article has been cited by other articles: C. Dunois-Larde, C. Capron, S. Fichelson, T. Bauer, E. Cramer-Borde, and D. Baruch Exposure of human megakaryocytes to high shear rates accelerates platelet production Blood, August 27, 2009; 114(9): 1875 - 1883. [Abstract] [Full Text] [PDF] A. E. Geddis The regulation of proplatelet production Haematologica, June 1, 2009; 94(6): 756 - 759. [Full Text] [PDF] P. Gresele, E. Falcinelli, S. Giannini, P. D'Adamo, A. D'Eustacchio, T. Corazzi, A. M. Mezzasoma, F. Di Bari, G. Guglielmini, L. Cecchetti, et al. Dominant inheritance of a novel integrin {beta}3 mutation associated with a hereditary macrothrombocytopenia and platelet dysfunction in two Italian families Haematologica, May 1, 2009; 94(5): 663 - 669. 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