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Blood, 24 September 2009, Vol. 114, No. 13, pp. 2793-2801. Prepublished online as a Blood First Edition Paper on July 21, 2009; DOI 10.1182/blood-2008-12-193490. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-12-193490v1 114/13/2793    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 Google Scholar Articles by Mazzucato, M. Articles by De Marco, L. PubMed PubMed Citation Articles by Mazzucato, M. Articles by De Marco, L. Related Collections Platelets and Thrombopoiesis Thrombosis and Hemostasis Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Distinct spatio-temporal Ca2+ signaling elicited by integrin 2β1 and glycoprotein VI under flow Mario Mazzucato1,*, Maria Rita Cozzi1,*, Monica Battiston1, Martine Jandrot-Perrus2, Maurizio Mongiat3, Patrizia Marchese4, Thomas J. Kunicki4, Zaverio M. Ruggeri4, and Luigi De Marco1 1 Department of Laboratory Medicine, Centro di Riferimento Oncologico (CRO) National Cancer Institute, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy; 2 Inserm E348, Faculté Xavier-Bichat, Paris, France; 3 Department of Experimental Oncology, Division 2, CRO National Cancer Institute, IRCCS, Aviano, Italy; and 4 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA We studied how integrin 2β1 and glycoprotein VI (GPVI) contribute to collagen-induced platelet activation under flow conditions by evaluating stable adhesion and intracellular Ca2+ concentration ([Ca2+]i) of FLUO 3-AM–labeled platelets perfused over acid-soluble type I or microfibrillar type VI collagen. Adhering platelets displayed 2 kinds of [Ca2+]i oscillations. Rapid -like peaks were unaffected by the membrane-impermeable Ca2+ chelator ethyleneglycoltetraacetic acid but abolished by membrane-permeable BAPTA-AM. Longer-lasting -like peaks were always preceded by at least one -like peak and abolished by intracellular or extracellular Ca2+ chelation. Inhibition of phosphatidylinositol 3-kinase or phospholipase C and modulation of cyclic nucleotides, but not blockage of adenosine diphosphate receptors, prevented both Ca2+ responses. Human or mouse platelets lacking GPVI function exhibited -like but not -like Ca2+ peaks, whereas those lacking 2β1 showed markedly reduced to absent -like and no -like Ca2+ peaks. Specific 2β1 ligation induced -like but not -like peaks. Thus, 2β1 may generate Ca2+ signals that are reinforced by GPVI and required for subsequent longer-lasting Ca2+ oscillation mediated by GPVI through transmembrane ion flux. Our results delineate a GPVI-independent signaling role of 2β1 in response to collagen stimulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Platelet integrin signaling: wherefore art thou? Alec A. Schmaier and Mark L. Kahn Blood 2009 114: 2571-2572. [Full Text] [PDF] This article has been cited by other articles: A. A. Schmaier and M. L. Kahn Platelet integrin signaling: wherefore art thou? Blood, September 24, 2009; 114(13): 2571 - 2572. [Full Text] [PDF]

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