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Blood, 19 November 2009, Vol. 114, No. 21, pp. 4729-4737. Prepublished online as a Blood First Edition Paper on August 19, 2009; DOI 10.1182/blood-2009-02-202721. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-02-202721v1 114/21/4729    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 Falet, H. Articles by Hartwig, J. H. PubMed PubMed Citation Articles by Falet, H. Articles by Hartwig, J. H. Related Collections Platelets and Thrombopoiesis Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Platelet-associated IgAs and impaired GPVI responses in platelets lacking WIP Hervé Falet1, Michael P. Marchetti1, Karin M. Hoffmeister1, Michel J. Massaad2, Raif S. Geha2, and John H. Hartwig1 1 Division of Translational Medicine, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School; and 2 Division of Immunology, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA The role of the Wiskott-Aldrich syndrome protein (WASp) in platelet function is unclear because platelets that lack WASp function normally. WASp constitutively associates with WASp-interacting protein (WIP) in resting and activated platelets. The role of WIP in platelet function was investigated using mice that lack WIP or WASp. WIP knockout (KO) platelets lack WASp and thus are double deficient. WIP KO mice have a thrombocytopenia, similar to WASp KO mice, resulting in part from enhanced platelet clearance. Most WIP KO, but not WASp KO, mice evolved platelet-associated immunoglobulins (Ig) of the IgA class, which normalize their platelet survival but diminish their glycoprotein VI (GPVI) responses. Protein tyrosine phosphorylation, including that of phospholipase C-2, and calcium mobilization are impaired in IgA-presenting WIP KO platelets stimulated through GPVI, resulting in defects in -granule secretion, integrin IIbβ3 activation, and actin assembly. The anti-GPVI antibody JAQ1 induces the irreversible loss of GPVI from circulating platelets in wild-type mice, but not in WIP KO mice that bear high levels of platelet-associated IgAs. Together, the data indicate that platelet-associated IgAs negatively modulate GPVI signaling and function in WIP KO mice. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Cracking the platelet WIP Alastair W. Poole Blood 2009 114: 4611-4612. [Full Text] [PDF] This article has been cited by other articles: A. W. Poole Cracking the platelet WIP Blood, November 19, 2009; 114(21): 4611 - 4612. [Full Text] [PDF]

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