Chen Zhu1,2, Qing-Yu Weng1,2, Ling-Ren Zhou1,2, Chao Cao3, Fei Li1, Yin-Fang Wu1, Yan-Ping Wu1, Miao Li1, Yue Hu1, Jia-Xin Shen1, Xue-Fang Xiong1,4, Fen Lan1, Li-Xia Xia1, Bin Zhang1, Hao Zhang1, Man Huang5, Song-Min Ying1, Hua-Hao Shen1,6,7, Zhi-Hua Chen1,7, Wen Li1,7. 1. Key Laboratory of Respiratory Disease of Zhejiang Province, Dept of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. 2. These authors contributed equally to this article. 3. Dept of Respiratory Medicine, Ningbo First Hospital, Ningbo, China. 4. Dept of Respiratory Medicine, The Central Hospital of Lishui City, Lishui, China. 5. Dept of Central Intensive Care Unit, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. 6. State Key Lab for Respiratory Diseases, Guangzhou, China. 7. These authors contributed equally to this article as lead authors and supervised the work.
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 ALI. 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 ALI.
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 ALI. 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 allergicCD101+ eosinophils exacerbated, the neutrophilic inflammation induced by LPS. Likewise, CD101 expression in eosinophils from ARDSpatients 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 ALI.
Authors: Cherie Alissa Lynch; Yizhan Guo; Zhongcheng Mei; Daniel Kreisel; Andrew E Gelman; Elizabeth A Jacobsen; Alexander Sasha Krupnick Journal: Transplantation Date: 2021-12-27 Impact factor: 5.385
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