2026-06-14T03:37:27Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/98052024-09-27T08:06:11Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Adrover, Jose M author Aroca-Crevillen, Alejandra author Crainiciuc, Georgiana author Ostos, Fernando author Rojas, Yeny author Rubio-Ponce, Andrea author Cilloniz, Catia author Bonzon-Kulichenko, Elena author Calvo, Enrique author Rico, Daniel author Moro, Maria Angeles author Weber, Christian author Lizasoaín, Ignacio author Torres, Antoni author Ruiz-Cabello, Jesus author Vazquez, Jesus author Hidalgo, Andres author 2020-02 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. Nat Immunol. 2020; 21(2):135-144 10.1038/s41590-019-0571-2 1529-2916 1529-2908 Nature immunology 31932813 http://hdl.handle.net/20.500.12105/9805 Programmed 'disarming' of the neutrophil proteome reduces the magnitude of inflammation