Author:
Zhu Chen,Weng Qing-Yu,Zhou Ling-Ren,Cao Chao,Li Fei,Wu Yin-Fang,Wu Yan-Ping,Li Miao,Hu Yue,Shen Jia-Xin,Xiong Xue-Fang,Lan Fen,Xia Li-Xia,Zhang Bin,Zhang Hao,Huang Man,Ying Song-Min,Shen Hua-Hao,Chen Zhi-Hua,Li Wen
Abstract
IntroductionAcute 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 ALI. Our objectives were to investigate the roles and molecular mechanisms of eosinophils in ALI.MethodsPulmonary 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.ResultsBlood 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.ConclusionsCollectively, our findings identify an uncovered function of native CD101− eosinophils in suppressing neutrophilic lung inflammation and suggest a potential therapeutic target for ALI.
Funder
National Natural Science Foundation of China
Publisher
European Respiratory Society (ERS)
Subject
Pulmonary and Respiratory Medicine
Cited by
37 articles.
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