Journal ArticleDOI
Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma
Duy Le Pham,Duy Le Pham,Ga-Young Ban,Seung-Hyun Kim,Yoo Seob Shin,Young Min Ye,Yong-Joon Chwae,Hae-Sim Park +7 more
TLDR
Autophagy and neutrophil extracellular DNA traps are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated.Abstract:
Background
Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated.
Objectives
We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs).
Methods
PBNs from patients with SA (n=30) and NSA (n=38) were treated with interleukin (IL)-8 (100 ng/ml). Autophagy (light chain 3-II expression) and NET production levels were evaluated by western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN).
Results
Untreated and IL-8-treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P<0.01). IL-8 increased autophagy and NET levels in PBNs from the SA group but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P<0.001). IL-8-induced NET production levels negatively were correlated with FEV1/FVC (r = 0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin-1, and IL-8 production from AECs. Higher levels of NET-induced ECP and EDN were released from PBEs in SA compared with NSA groups.
Conclusions & Clinical Relevance
Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA.
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Citations
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Journal ArticleDOI
Autophagy and inflammation in chronic respiratory disease.
TL;DR: The role of autophagy in driving and regulating inflammatory responses of the lung in chronic lung diseases with a focus on potential avenues for therapeutic targeting is discussed.
Journal ArticleDOI
Complex interplay between autophagy and oxidative stress in the development of pulmonary disease.
Wojciech Ornatowski,Qing Lu,Manivannan Yegambaram,Alejandro E. Garcia,Evgeny A. Zemskov,Emin Maltepe,Jeffrey R. Fineman,Ting Wang,Stephen M. Black +8 more
TL;DR: This review highlights the current understanding on the interplay between ROS and autophagy in the development of pulmonary disease and suggests a central role for autophile as a mammalian oxidative stress response and its interrelationship to other stress defense systems.
Journal ArticleDOI
Extracellular DNA, Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma.
Marrah E. Lachowicz-Scroggins,Eleanor M. Dunican,Annabelle R. Charbit,Wilfred W. Raymond,Mark R. Looney,Michael C. Peters,Erin D. Gordon,Prescott G. Woodruff,Emma Lefrançais,Brenda R. Phillips,David T. Mauger,Suzy A. A. Comhair,Serpil C. Erzurum,Mats W. Johansson,Nizar N. Jarjour,Andrea M. Coverstone,Mario Castro,Annette T. Hastie,Eugene R. Bleecker,Merritt L. Fajt,Sally E. Wenzel,Elliot Israel,Bruce D. Levy,John V. Fahy +23 more
TL;DR: High extracellular DNA concentrations in sputum mark a subset of patients with more severe asthma who have NETs and markers of inflammasome activation in their airways, as well as in in vitro studies, NETs caused cytotoxicity in airway epithelial cells that was prevented by disruption of NETs with DNase.
Journal ArticleDOI
Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment
TL;DR: The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection, and blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.
Journal ArticleDOI
Neutrophil extracellular traps in breast cancer and beyond: current perspectives on NET stimuli, thrombosis and metastasis, and clinical utility for diagnosis and treatment
TL;DR: The mechanisms by which NETs may form in the tumor microenvironment and circulation, including the crosstalk between neutrophils, tumor cells, endothelial cells, and platelets as well as the role of cancer-associated extracellular vesicles in modulating neutrophil behavior and NET extrusion are outlined.
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TL;DR: A set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes are presented.