Activated αiibβ3 on platelets mediates flow-dependent netosis via slc44a2

74Citations
Citations of this article
72Readers
Mendeley users who have this article in their library.

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 Ib-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.

Cite

CITATION STYLE

APA

Constantinescu-Bercu, A., Grassi, L., Frontini, M., Salles-Crawley, I. I., Woollard, K. J., & Crawley, J. T. B. (2020). Activated αiibβ3 on platelets mediates flow-dependent netosis via slc44a2. ELife, 9. https://doi.org/10.7554/eLife.53353

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free