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dc.contributor.authorConstantinescu-Bercu, Adela
dc.contributor.authorGrassi, Luigi
dc.contributor.authorFrontini, Mattia
dc.contributor.authorSalles-Crawley, Isabelle I
dc.contributor.authorWoollard, Kevin
dc.contributor.authorCrawley, James TB
dc.date.accessioned2020-05-28T05:11:40Z
dc.date.available2020-05-28T05:11:40Z
dc.date.issued2020-04-21
dc.date.submitted2019-11-06
dc.identifier.other53353
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/305836
dc.description.abstractPlatelet-neutrophil interactions are important for innate immunity, but also contribute to the pathogenesis of deep vein thrombosis, myocardial infarction and stroke. Here we report that, under flow, von Willebrand factor/glycoprotein Ibα-dependent platelet ‘priming’ induces integrin αIIbβ3 activation that, in turn, mediates neutrophil and T-cell binding. Binding of platelet αIIbβ3 to SLC44A2 on neutrophils leads to mechanosensitive-dependent production of highly prothrombotic neutrophil extracellular traps. A polymorphism in SLC44A2 (rs2288904-A) present in 22% of the population causes an R154Q substitution in an extracellular loop of SLC44A2 that is protective against venous thrombosis results in severely impaired binding to both activated αIIbβ3 and VWF-primed platelets. This was confirmed using neutrophils homozygous for the SLC44A2 R154Q polymorphism. Taken together, these data reveal a previously unreported mode of platelet-neutrophil crosstalk, mechanosensitive NET production, and provide mechanistic insight into the protective effect of the SLC44A2 rs2288904-A polymorphism in venous thrombosis.
dc.languageen
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch Article
dc.subjectCell Biology
dc.subjectHuman Biology and Medicine
dc.subjectVWF
dc.subjectαiibβ3
dc.subjectplatelet
dc.subjectneutrophil
dc.subjectSLC44A2
dc.subjectNETosis
dc.subjectHuman
dc.titleActivated α IIb β 3 on platelets mediates flow-dependent NETosis via SLC44A2
dc.typeArticle
dc.date.updated2020-05-28T05:11:39Z
prism.publicationNameeLife
prism.volume9
dc.identifier.doi10.17863/CAM.52916
dcterms.dateAccepted2020-04-20
rioxxterms.versionofrecord10.7554/elife.53353
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Ginsburg, David
datacite.contributor.supervisorsenior_editor: Rath, Satyajit
dc.contributor.orcidConstantinescu-Bercu, Adela [0000-0002-1274-2867]
dc.contributor.orcidWoollard, Kevin [0000-0002-9839-5463]
dc.contributor.orcidCrawley, James TB [0000-0002-6723-7841]
dc.identifier.eissn2050-084X
pubs.funder-project-idBritish Heart Foundation (FS/15/65/32036)
pubs.funder-project-idBritish Heart Foundation (PG/17/22/32868)
pubs.funder-project-idBritish Heart Foundation (FS/18/53/33863)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)