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oai:repisalud.isciii.es:20.500.12105/51762024-09-27T09:47:49Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Rossaint, Jan author Kuehne, Katharina author Skupski, Jennifer author Van Aken, Hugo author Looney, Mark R. author Hidalgo, Andres author Zarbock, Alexander author 2016 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 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. Nat Commun. 2016; 7:13464 10.1038/ncomms13464 2041-1723 Nature Communicacions 27845343 http://hdl.handle.net/20.500.12105/5176 ACUTE LUNG INJURY GLYCOPROTEIN IB-ALPHA RESPIRATORY-DISTRESS-SYNDROME P-SELECTIN POLYMORPHONUCLEAR LEUKOCYTES PROSTAGLANDIN E-2 INTEGRIN MAC-1 UP-REGULATION KAPPA-B INFLAMMATION Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response