Rossaint, JanKuehne, KatharinaSkupski, JenniferVan Aken, HugoLooney, Mark R.Hidalgo, AndresZarbock, Alexander2017-10-202017-10-202016Nat Commun. 2016; 7:134642041-1723http://hdl.handle.net/20.500.12105/5176The 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 Ib alpha (GPIb alpha)-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 A(2) (TxA(2)). Finally, platelet-derived-TxA(2) 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.engVoRhttp://creativecommons.org/licenses/by/4.0/ACUTE LUNG INJURYGLYCOPROTEIN IB-ALPHARESPIRATORY-DISTRESS-SYNDROMEP-SELECTINPOLYMORPHONUCLEAR LEUKOCYTESPROSTAGLANDIN E-2INTEGRIN MAC-1UP-REGULATIONKAPPA-BINFLAMMATIONAtribución 4.0 Internacional27845343710.1038/ncomms13464Nature Communicacionsopen access