Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/5176
Título
Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response
Autor(es)
Fecha de publicación
2016
Cita
Nat Commun. 2016; 7:13464
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
Palabras clave
ACUTE LUNG INJURY | GLYCOPROTEIN IB-ALPHA | RESPIRATORY-DISTRESS-SYNDROME | P-SELECTIN | POLYMORPHONUCLEAR LEUKOCYTES | PROSTAGLANDIN E-2 | INTEGRIN MAC-1 | UP-REGULATION | KAPPA-B | INFLAMMATION
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![Acceso Abierto Acceso Abierto](/themes/Mirage2/images/openAccess.png)
- Nombre:
- DirectedTransportOfNeutrohil-d ...
- Tamaño:
- 13.57Mb
- Formato:
- Video QuickTime