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Nat Commun. 2016 Nov 15;7:13464. doi: 10.1038/ncomms13464.

Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response.

Author information

1
Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, 48149 Münster, Germany.
2
Department of Medicine, University of California, San Francisco, California 94143, USA.
3
Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, 80336 Munich, Germany.
4
Area of Cell and Developmental Biology, CNIC, 28029 Madrid, Spain.

Abstract

The innate immune response to bacterial infections requires the interaction of neutrophils and platelets. Here, we show that a multistep reciprocal crosstalk exists between these two cell types, ultimately facilitating neutrophil influx into the lung to eliminate infections. Activated platelets adhere to intravascular neutrophils through P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1)-mediated binding, a primary interaction that allows platelets glycoprotein Ibα (GPIbα)-induced generation of neutrophil-derived extracellular vesicles (EV). EV production is directed by exocytosis and allows shuttling of arachidonic acid into platelets. EVs are then specifically internalized into platelets in a Mac1-dependent fashion, and relocated into intracellular compartments enriched in cyclooxygenase1 (Cox1), an enzyme processing arachidonic acid to synthesize thromboxane A2 (TxA2). Finally, platelet-derived-TxA2 elicits a full neutrophil response by inducing the endothelial expression of ICAM-1, intravascular crawling, and extravasation. We conclude that critical substrate-enzyme pairs are compartmentalized in neutrophils and platelets during steady state limiting non-specific inflammation, but bacterial infection triggers regulated EV shuttling resulting in robust inflammation and pathogen clearance.

PMID:
27845343
PMCID:
PMC5116072
DOI:
10.1038/ncomms13464
[Indexed for MEDLINE]
Free PMC Article

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