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

Jan Rossaint, Katharina Kühne, Jennifer Skupski, Hugo Van Aken, Mark R. Looney, Andres Hidalgo and Alexander Zarbock ()
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Jan Rossaint: Intensive Care and Pain Medicine, University Hospital Münster
Katharina Kühne: Intensive Care and Pain Medicine, University Hospital Münster
Jennifer Skupski: Intensive Care and Pain Medicine, University Hospital Münster
Hugo Van Aken: Intensive Care and Pain Medicine, University Hospital Münster
Mark R. Looney: University of California
Andres Hidalgo: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University
Alexander Zarbock: Intensive Care and Pain Medicine, University Hospital Münster

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13464

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