Delayed neutrophil apoptosis may enhance NET formation in ARDS

Chao Song; Haitao Li; Zhi Mao; Ling Peng; Ben Liu; Fengyu Lin; Yi Li; Minhui Dai; Yanhui Cui; Yuhao Zhao; Duoduo Han; Lingli Chen; Xun Huang; Pinhua Pan

doi:10.1186/s12931-022-02065-y

Respiratory Research (Jun 2022)

Delayed neutrophil apoptosis may enhance NET formation in ARDS

Chao Song,
Haitao Li,
Zhi Mao,
Ling Peng,
Ben Liu,
Fengyu Lin,
Yi Li,
Minhui Dai,
Yanhui Cui,
Yuhao Zhao,
Duoduo Han,
Lingli Chen,
Xun Huang,
Pinhua Pan

Affiliations

Chao Song: Infection Control Center, Xiangya Hospital, Central South University
Haitao Li: Cancer Hospital of Hunan Province
Zhi Mao: Shenzhen Third People’s Hospital of Guangdong Province
Ling Peng: Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University
Ben Liu: Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University
Fengyu Lin: Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University
Yi Li: Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University
Minhui Dai: Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University
Yanhui Cui: Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University
Yuhao Zhao: Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University
Duoduo Han: Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University
Lingli Chen: Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University
Xun Huang: Infection Control Center, Xiangya Hospital, Central South University
Pinhua Pan: Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University

DOI: https://doi.org/10.1186/s12931-022-02065-y
Journal volume & issue: Vol. 23, no. 1
pp. 1 – 15

Abstract

Read online

Abstract 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.

Published in Respiratory Research

ISSN: 1465-9921 (Print); 1465-993X (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the respiratory system
Website: https://respiratory-research.biomedcentral.com/

About the journal

Abstract

Keywords