Homeostatic and early-recruited CD101- eosinophils suppress endotoxin-induced acute lung injury
- 1 November 2020
- journal article
- research article
- Published by European Respiratory Society (ERS) in European Respiratory Journal
- Vol. 56 (5), 1902354
- https://doi.org/10.1183/13993003.02354-2019
Abstract
Introduction: Acute lung injury (ALI) is a fatal but undertreated condition with severe neutrophilic inflammation, although little is known about the functions of eosinophils in the pathogenesis of ALL Our objectives were to investigate the roles and molecular mechanisms of eosinophils in ALI. Methods: Pulmonary eosinophils were identified by flow cytometry. Mice with abundant or deficient eosinophils were used. Cellularity of eosinophils and neutrophils in bronchoalveolar lavage fluid, inflammatory assessment, and survival rate were determined. Human samples were also used for validating experimental results. Results: Blood eosinophils were increased in surviving patients with acute respiratory distress syndrome (ARDS) independent of corticosteroid usage. There existed homeostatic eosinophils in lung parenchyma in mice and these homeostatic eosinophils, originating from the bone marrow, were predominantly CD101(-). More CD101(-) eosinophils could be recruited earlier than lipopolysaccharide (LPS)-initiated neutrophilic inflammation. Loss of eosinophils augmented LPS-induced pulmonary injury. Homeostatic CD101(-) eosinophils ameliorated, while allergic CD101(+) eosinophils exacerbated, the neutrophilic inflammation induced by LPS. Likewise, CD101(-) expression in eosinophils from ARDS patients did not differ from healthy subjects. Mechanistically, CD101(-) eosinophils exhibited higher levels of Alox15 and Protectin D1. Administration of Protectin D1 isomer attenuated the neutrophilic inflammation. Conclusions: Collectively, our findings identify an uncovered function of native CD101(-) eosinophils in suppressing neutrophilic lung inflammation and suggest a potential therapeutic target for ALT.Funding Information
- National Natural Science Foundation of China (2015CB553405, 2016YFA0501602, 81420108001, 81490532, 91642202)
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