Programmed ‘disarming’ of the neutrophil proteome reduces the magnitude of inflammation

Autor: José M. Adrover, Fernando Ostos, Enrique Calvo, Andrea Rubio-Ponce, Christian Weber, Elena Bonzón-Kulichenko, Yeny Rojas-Vega, Ignacio Lizasoain, Daniel Rico, Antoni Torres, Andrés Hidalgo, María A. Moro, Jesús Vázquez, Georgiana Crainiciuc, Alejandra Aroca-Crevillen, Jesús Ruiz-Cabello, Catia Cilloniz
Přispěvatelé: Fundación La Marató TV3, Ministerio de Ciencia, Innovación y Universidades (España), Fundación La Caixa, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Instituto de Salud Carlos III, Wellcome Trust, Deutsche Forschungsgemeinschaft (Alemania), European Research Council, Fundación ProCNIC, Biochemie, RS: Carim - B01 Blood proteins & engineering
Jazyk: angličtina
Předmět:
Zdroj: Nature Immunology
Nature Immunology, 21(2), 135-144. Nature Publishing Group
ISSN: 1529-2916
1529-2908
DOI: 10.1038/s41590-019-0571-2
Popis: 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. We thank members of the Comparative Medicine Unit and Advanced Microscopy Unit at CNIC. This study was supported by Intramural grants from the Severo Ochoa program (IGP-SO), a grant from Fundació La Marató de TV3 (120/C/2015-20153032), grant SAF2015-65607-R from Ministerio de Ciencia, Investigacion y Universidades (MCIU) with cofunding from Fondo Europeo de Desarrollo Regional, grant RTI2018-095497-B-I00 from MCIU and HR17_00527 from Fundación La Caixa (to A.H.), and fellowship BES-2013-065550 from MCIU (to J.M.A.), fellowship from La Caixa Foundation (ID 100010434, code LCF/BQ/DR19/11740022, to A.A.-C.) and fellowship Health-PERIS 2016–2020 (to C.C.) Funds were also obtained from Instituto de Salud Carlos III (FIS PI17/01601, to I.L.) and SAF2015-68632-R from MCIU (to M.A.M.); Wellcome Trust Seed Award in Science (206103/Z/17/Z, to D.R.), SFB1123-A1/A10 from Deutsche Forschungsgemeinschaft and ERC-AdG 692511 (to C.W.); SAF2017-84494-C2-R and Programa Red Guipuzcoana de Ciencia, Tecnología e Información 2018-CIEN-000058-01 (to J.R.-C.). Work at CIC biomaGUNE was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (MDM-2017-0720). C.W. is a van de Laar professor of atherosclerosis. The CNIC is supported by the MCIU and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505). Sí
Databáze: OpenAIRE
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