-------A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS--.

Autor:	Reyes L; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., A Sanchez-Garcia M; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Morrison T; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Howden AJM; Division of Cell Signalling and Immunology, University of Dundee, Dundee, DD1 5EH, UK., Watts ER; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Arienti S; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Sadiku P; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Coelho P; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Mirchandani AS; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Zhang A; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Hope D; Anaesthesia, Critical Care and Pain, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, EH16 4TJ, UK., Clark SK; Anaesthesia, Critical Care and Pain, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, EH16 4TJ, UK., Singleton J; Anaesthesia, Critical Care and Pain, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, EH16 4TJ, UK., Johnston S; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Grecian R; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Poon A; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., McNamara S; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Harper I; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Fourman MH; Anaesthesia, Critical Care and Pain, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, EH16 4TJ, UK., Brenes AJ; Division of Cell Signalling and Immunology, University of Dundee, Dundee, DD1 5EH, UK.; Centre for Gene Regulation and Expression, University of Dundee, Dundee, DD1 5EH, UK., Pathak S; Division of Cell Signalling and Immunology, University of Dundee, Dundee, DD1 5EH, UK., Lloyd A; Division of Cell Signalling and Immunology, University of Dundee, Dundee, DD1 5EH, UK., Blanco GR; The University of Edinburgh MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK., von Kriegsheim A; The University of Edinburgh MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK., Ghesquiere B; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium., Vermaelen W; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium., Cologna CT; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium., Dhaliwal K; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Hirani N; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.; NHS Lothian, Respiratory Medicine, Edinburgh Lung Fibrosis Clinic, Royal Infirmary, Edinburgh, EH16 4SA, UK., Dockrell DH; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Whyte MKB; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK., Griffith D; Anaesthesia, Critical Care and Pain, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, EH16 4TJ, UK., Cantrell DA; Division of Cell Signalling and Immunology, University of Dundee, Dundee, DD1 5EH, UK., Walmsley SR; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
Jazyk:	angličtina
Zdroj:	Wellcome open research [Wellcome Open Res] 2021 May 20; Vol. 6, pp. 38. Date of Electronic Publication: 2021 May 20 (Print Publication: 2021).
DOI:	10.12688/wellcomeopenres.16584.2
Abstrakt:	Background: Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation. Results: Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population, it does not impact upon prothrombotic hyperinflammatory neutrophil signatures. Conclusions: Given the crucial role of neutrophils in ARDS and the evidence of a disordered myeloid response observed in COVID-19 patients, this work maps the molecular basis for neutrophil reprogramming in the distinct clinical entities of COVID-19 and non-COVID-19 ARDS. Competing Interests: No competing interests were disclosed. (Copyright: © 2021 Reyes L et al.)
Databáze:	MEDLINE
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