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.
Abstract
Eosinophils, a type of immune cell easily overlooked in nonallergic inflammatory diseases, could reside and be rapidly recruited into lungs to suppress endotoxin-induced acute lung injury https://bit.ly/3dyvCaD
Footnotes
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Author contributions: C. Zhu, C. Cao, S-M. Ying, Z-H. Chen, H-H. Shen and W. Li designed and analysed the studies. C. Zhu, Q-Y. Weng and L-R. Zhou performed the experiments. F. Li contributed to the isolation of eosinophils from NJ.1638 mice. Y-F. Wu, Y-P. Wu, M. Li and J-X. Shen assisted with animal breeding and sacrifice of the ALI and OVA models. C. Cao, Y. Hu, F. Lan, L-X. Xia, B. Zhang, H. Zhang, M. Huang and X-F. Xiong contributed to the collection of human samples. C. Zhu, Z-H. Chen and S-M. Ying drafted the article, and L-R. Zhou with Q-Y. Weng proofread the manuscript. All the experiments were undertaken under the supervision of H-H. Shen, Z-H. Chen and W. Li. All authors approved the final manuscript.
Conflict of interest: C. Zhu has nothing to disclose.
Conflict of interest: Q-Y. Weng has nothing to disclose.
Conflict of interest: L-R. Zhou has nothing to disclose.
Conflict of interest: C. Cao has nothing to disclose.
Conflict of interest: F. Li has nothing to disclose.
Conflict of interest: Y-F. Wu has nothing to disclose.
Conflict of interest: Y-P. Wu has nothing to disclose.
Conflict of interest: M. Li has nothing to disclose.
Conflict of interest: Y. Hu has nothing to disclose.
Conflict of interest: J-X. Shen has nothing to disclose.
Conflict of interest: X-F. Xiong has nothing to disclose.
Conflict of interest: F. Lan has nothing to disclose.
Conflict of interest: L-X. Xia has nothing to disclose.
Conflict of interest: B. Zhang has nothing to disclose.
Conflict of interest: H. Zhang has nothing to disclose.
Conflict of interest: M. Huang has nothing to disclose.
Conflict of interest: S-M. Ying has nothing to disclose.
Conflict of interest: H-H. Shen has nothing to disclose.
Conflict of interest: Z-H. Chen has nothing to disclose.
Conflict of interest: W. Li has nothing to disclose.
Support statement: This work was financially supported by the Major Project of the National Natural Science Foundation of China (NSFC; 91642202 to W. Li, 81490532 to H-H. Shen), International Cooperation Project of the NSFC (81420108001 to H-H. Shen), the National Key R&D Program of China (2016YFA0501602 to Z-H. Chen), and the Key Project of Chinese National Programs for Fundamental Research and Development (973 program, 2015CB553405 to Z-H. Chen). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received March 22, 2019.
- Accepted June 1, 2020.
- Copyright ©ERS 2020