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Activated αIIbβ3 on platelets mediates flow-dependent NETosis via SLC44A2.

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Title: Activated αIIbβ3 on platelets mediates flow-dependent NETosis via SLC44A2.
Authors: Constantinescu-Bercu, A
Grassi, L
Frontini, M
Salles-Crawley, II
Woollard, K
Crawley, JT
Item Type: Journal Article
Abstract: Platelet-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 Iba-dependent platelet 'priming' induces integrin aIIbb3 activation that, in turn, mediates neutrophil and T-cell binding. Binding of platelet aIIbb3 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 aIIbb3 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.
Issue Date: 21-Apr-2020
Date of Acceptance: 20-Apr-2020
URI: http://hdl.handle.net/10044/1/79600
DOI: 10.7554/eLife.53353
ISSN: 2050-084X
Publisher: eLife Sciences Publications Ltd
Journal / Book Title: eLife
Volume: 9
Copyright Statement: © 2020, Constantinescu-Bercu et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Sponsor/Funder: British Heart Foundation
British Heart Foundation
Funder's Grant Number: PG/17/22/32868
FS/15/65/32036
Keywords: cell biology
human
human biology
medicine
cell biology
human
human biology
medicine
0601 Biochemistry and Cell Biology
Publication Status: Published
Conference Place: England
Open Access location: https://elifesciences.org/articles/53353
Article Number: ARTN e53353
Appears in Collections:Department of Immunology and Inflammation