| Platelet ITAM signaling is critical for vascular integrity in inflammation. | |
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MedLine Citation:
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PMID: 23348738 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Platelets play a critical role in maintaining vascular integrity during inflammation, but little is known about the underlying molecular mechanisms. Here we report that platelet immunoreceptor tyrosine activation motif (ITAM) signaling, but not GPCR signaling, is critical for the prevention of inflammation-induced hemorrhage. To generate mice with partial or complete defects in these signaling pathways, we developed a protocol for adoptive transfer of genetically and/or chemically inhibited platelets into thrombocytopenic (TP) mice. Unexpectedly, platelets with impaired GPCR signaling, a crucial component of platelet plug formation and hemostasis, were indistinguishable from WT platelets in their ability to prevent hemorrhage at sites of inflammation. In contrast, inhibition of GPVI or genetic deletion of Clec2, the only ITAM receptors expressed on mouse platelets, significantly reduced the ability of platelets to prevent inflammation-induced hemorrhage. Moreover, transfusion of platelets without ITAM receptor function or platelets lacking the adapter protein SLP-76 into TP mice had no significant effect on vascular integrity during inflammation. These results indicate that the control of vascular integrity is a major function of immune-type receptors in platelets, highlighting a potential clinical complication of novel antithrombotic agents directed toward the ITAM signaling pathway. |
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Authors:
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Yacine Boulaftali; Paul R Hess; Todd M Getz; Agnieszka Cholka; Moritz Stolla; Nigel Mackman; A Phillip Owens; Jerry Ware; Mark L Kahn; Wolfgang Bergmeier |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2013-01-25 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 123 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-04-19 Completed Date: 2013-05-13 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 908-16 Citation Subset: AIM; IM |
Affiliation:
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McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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antagonists & inhibitors,
blood Adoptive Transfer Animals Blood Platelets / physiology* Blood Vessels / physiopathology* Hemostasis Inflammation / blood*, physiopathology* Lectins, C-Type / deficiency, genetics Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Phosphoproteins / antagonists & inhibitors, blood Platelet Membrane Glycoproteins / antagonists & inhibitors, physiology Receptors, G-Protein-Coupled / blood, physiology Receptors, Thrombin / blood, deficiency, genetics Signal Transduction Thrombocytopenia / blood, physiopathology |
| Grant Support | |
ID/Acronym/Agency:
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F32 HL099175/HL/NHLBI NIH HHS; HL006350/HL/NHLBI NIH HHS; HL072798/HL/NHLBI NIH HHS; HL106009/HL/NHLBI NIH HHS; HL50545/HL/NHLBI NIH HHS; R01 HL067311/HL/NHLBI NIH HHS; R01 HL094594/HL/NHLBI NIH HHS; R01 HL094594/HL/NHLBI NIH HHS; R01 HL103432/HL/NHLBI NIH HHS; R01 HL106009/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/CLEC-2 protein, mouse; 0/Lectins, C-Type; 0/Phosphoproteins; 0/Platelet Membrane Glycoproteins; 0/Receptors, G-Protein-Coupled; 0/Receptors, Thrombin; 0/SLP-76 signal Transducing adaptor proteins; 0/platelet membrane glycoprotein VI; 0/protease-activated receptor 4 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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