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Delayed neutrophil apoptosis may enhance NET formation in ARDS
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a neutrophil-associated disease. Delayed neutrophil apoptosis and increased levels of neutrophil extracellular traps (NETs) have been described in ARDS. We aimed to investigate the relationship between these phenomena and their potential as i...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190136/ https://www.ncbi.nlm.nih.gov/pubmed/35698192 http://dx.doi.org/10.1186/s12931-022-02065-y |
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author | Song, Chao Li, Haitao Mao, Zhi Peng, Ling Liu, Ben Lin, Fengyu Li, Yi Dai, Minhui Cui, Yanhui Zhao, Yuhao Han, Duoduo Chen, Lingli Huang, Xun Pan, Pinhua |
author_facet | Song, Chao Li, Haitao Mao, Zhi Peng, Ling Liu, Ben Lin, Fengyu Li, Yi Dai, Minhui Cui, Yanhui Zhao, Yuhao Han, Duoduo Chen, Lingli Huang, Xun Pan, Pinhua |
author_sort | Song, Chao |
collection | PubMed |
description | BACKGROUND: Acute respiratory distress syndrome (ARDS) is a neutrophil-associated disease. Delayed neutrophil apoptosis and increased levels of neutrophil extracellular traps (NETs) have been described in ARDS. We aimed to investigate the relationship between these phenomena and their potential as inflammation drivers. We hypothesized that delayed neutrophil apoptosis might enhance NET formation in ARDS. METHOD: Our research was carried out in three aspects: clinical research, animal experiments, and in vitro experiments. First, we compared the difference between neutrophil apoptosis and NET levels in healthy controls and patients with ARDS and analyzed the correlation between neutrophil apoptosis and NET levels in ARDS. Then, we conducted animal experiments to verify the effect of neutrophil apoptosis on NET formation in Lipopolysaccharide-induced acute lung injury (LPS-ALI) mice. Furthermore, this study explored the relationship between neutrophil apoptosis and NETs at the cellular level. Apoptosis was assessed using morphological analysis, flow cytometry, and western blotting. NET formation was determined using immunofluorescence, PicoGreen assay, SYTOX Green staining, and western blotting. RESULTS: ARDS neutrophils lived longer because of delayed apoptosis, and the cyclin-dependent kinase inhibitor, AT7519, reversed this phenomenon both in ARDS neutrophils and neutrophils in bronchoalveolar lavage fluid (BALF) of LPS-ALI mice. Neutrophils in a medium containing pro-survival factors (LPS or GM-CSF) form more NETs, which can also be reversed by AT7519. Tissue damage can be reduced by promoting neutrophil apoptosis. CONCLUSIONS: Neutrophils with extended lifespan in ARDS usually enhance NET formation, which aggravates inflammation. Enhancing neutrophil apoptosis in ARDS can reduce the formation of NETs, inhibit inflammation, and consequently alleviate ARDS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02065-y. |
format | Online Article Text |
id | pubmed-9190136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91901362022-06-14 Delayed neutrophil apoptosis may enhance NET formation in ARDS Song, Chao Li, Haitao Mao, Zhi Peng, Ling Liu, Ben Lin, Fengyu Li, Yi Dai, Minhui Cui, Yanhui Zhao, Yuhao Han, Duoduo Chen, Lingli Huang, Xun Pan, Pinhua Respir Res Research BACKGROUND: Acute respiratory distress syndrome (ARDS) is a neutrophil-associated disease. Delayed neutrophil apoptosis and increased levels of neutrophil extracellular traps (NETs) have been described in ARDS. We aimed to investigate the relationship between these phenomena and their potential as inflammation drivers. We hypothesized that delayed neutrophil apoptosis might enhance NET formation in ARDS. METHOD: Our research was carried out in three aspects: clinical research, animal experiments, and in vitro experiments. First, we compared the difference between neutrophil apoptosis and NET levels in healthy controls and patients with ARDS and analyzed the correlation between neutrophil apoptosis and NET levels in ARDS. Then, we conducted animal experiments to verify the effect of neutrophil apoptosis on NET formation in Lipopolysaccharide-induced acute lung injury (LPS-ALI) mice. Furthermore, this study explored the relationship between neutrophil apoptosis and NETs at the cellular level. Apoptosis was assessed using morphological analysis, flow cytometry, and western blotting. NET formation was determined using immunofluorescence, PicoGreen assay, SYTOX Green staining, and western blotting. RESULTS: ARDS neutrophils lived longer because of delayed apoptosis, and the cyclin-dependent kinase inhibitor, AT7519, reversed this phenomenon both in ARDS neutrophils and neutrophils in bronchoalveolar lavage fluid (BALF) of LPS-ALI mice. Neutrophils in a medium containing pro-survival factors (LPS or GM-CSF) form more NETs, which can also be reversed by AT7519. Tissue damage can be reduced by promoting neutrophil apoptosis. CONCLUSIONS: Neutrophils with extended lifespan in ARDS usually enhance NET formation, which aggravates inflammation. Enhancing neutrophil apoptosis in ARDS can reduce the formation of NETs, inhibit inflammation, and consequently alleviate ARDS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02065-y. BioMed Central 2022-06-13 2022 /pmc/articles/PMC9190136/ /pubmed/35698192 http://dx.doi.org/10.1186/s12931-022-02065-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Song, Chao Li, Haitao Mao, Zhi Peng, Ling Liu, Ben Lin, Fengyu Li, Yi Dai, Minhui Cui, Yanhui Zhao, Yuhao Han, Duoduo Chen, Lingli Huang, Xun Pan, Pinhua Delayed neutrophil apoptosis may enhance NET formation in ARDS |
title | Delayed neutrophil apoptosis may enhance NET formation in ARDS |
title_full | Delayed neutrophil apoptosis may enhance NET formation in ARDS |
title_fullStr | Delayed neutrophil apoptosis may enhance NET formation in ARDS |
title_full_unstemmed | Delayed neutrophil apoptosis may enhance NET formation in ARDS |
title_short | Delayed neutrophil apoptosis may enhance NET formation in ARDS |
title_sort | delayed neutrophil apoptosis may enhance net formation in ards |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190136/ https://www.ncbi.nlm.nih.gov/pubmed/35698192 http://dx.doi.org/10.1186/s12931-022-02065-y |
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