Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/9805
Programmed 'disarming' of the neutrophil proteome reduces the magnitude of inflammation
Adrover, Jose M CNIC | Aroca-Crevillen, Alejandra CNIC | Crainiciuc, Georgiana CNIC | Ostos, Fernando | Rojas, Yeny CNIC | Rubio-Ponce, Andrea CNIC | Cilloniz, Catia | Bonzon-Kulichenko, Elena CNIC | Calvo, Enrique CNIC | Rico, Daniel CNIC | Moro, Maria Angeles | Weber, Christian | Lizasoaín, Ignacio | Torres, Antoni | Ruiz-Cabello, Jesus CNIC | Vazquez, Jesus CNIC | Hidalgo, Andrés CNIC
Nat Immunol. 2020; 21(2):135-144
The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.
Animals | Cell Degranulation | Circadian Rhythm | Cytoplasmic Granules | Extracellular Traps | Humans | Inflammation | Mice | Neutrophils | Pneumonia | Proteome | Respiratory Distress Syndrome, Adult
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