Neutrophil extracellular traps (NETs) in COPD: A potential novel mechanism for host damage in acute exacerbations

Pullan, J. M.; Greenwood, Hannah; Walton, Georgia M; Stockley, Robert A.; Sapey, Elizabeth

doi:10.1183/13993003.congress-2015.pa5055

Cited by 11 publications

(9 citation statements)

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“…Interestingly, the most recent study of NETs in COPD shows a correlation between NET complexes in sputum and microbial diversity, in particular a dominance of haemophilus species, whereby more than 40% haemophilus species within the lung microbiome were found to be associated with significantly greater DNA-elastase complexes 78 . Despite this, neutrophils isolated from the blood of patients with exacerbations of COPD have been shown to have a reduced ability to undergo NETosis compared with both stable patients and healthy controls, despite the increased presence of cell-free DNA in plasma 79 . This seems counterintuitive but it is possible that the clearance of NETs by DNases 80 is impaired in COPD or that only a proportion of cells are able to produce NETs (a phenotype of cell) but this remains unknown.…”

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

Understanding the role of neutrophils in chronic inflammatory airway disease

et al. 2019

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Airway neutrophilia is a common feature of many chronic inflammatory lung diseases and is associated with disease progression, often regardless of the initiating cause. Neutrophils and their products are thought to be key mediators of the inflammatory changes in the airways of patients with chronic obstructive pulmonary disease (COPD) and have been shown to cause many of the pathological features associated with disease, including emphysema and mucus hypersecretion. Patients with COPD also have high rates of bacterial colonisation and recurrent infective exacerbations, suggesting that neutrophil host defence mechanisms are impaired, a concept supported by studies showing alterations to neutrophil migration, degranulation and reactive oxygen species production in cells isolated from patients with COPD. Although the role of neutrophils is best described in COPD, many of the pathological features of this disease are not unique to COPD and also feature in other chronic inflammatory airway diseases, including asthma, cystic fibrosis, alpha-1 anti-trypsin deficiency, and bronchiectasis. There is increasing evidence for immune cell dysfunction contributing to inflammation in many of these diseases, focusing interest on the neutrophil as a key driver of pulmonary inflammation and a potential therapeutic target than spans diseases. This review discusses the evidence for neutrophilic involvement in COPD and also considers their roles in alpha-1 anti-trypsin deficiency, bronchiectasis, asthma, and cystic fibrosis. We provide an in-depth assessment of the role of the neutrophil in each of these conditions, exploring recent advances in understanding, and finally discussing the possibility of common mechanisms across diseases.

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Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

Understanding the role of neutrophils in chronic inflammatory airway disease

et al. 2019

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“…Similarly, there is conflicting evidence of NETosis; increased quantities of NETs and NET-producing neutrophils are observed in the sputum of both stable and exacerbating COPD patients (131,132), however when isolated from blood, neutrophils of exacerbating patients demonstrate attenuated NET-producing ability (133). A potential explanation for this is an impaired clearance of NETs by DNAses(119) rather than increased production, but this is currently unexplored.…”

Section: Neutrophil Functions In Health and Copdmentioning

confidence: 99%

Neutrophilic Inflammation in the Pathogenesis of Chronic Obstructive Pulmonary Disease

Butler

Walton

Sapey

2018

COPD: Journal of Chronic Obstructive Pulmonary Disease

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Current paradigms of chronic obstructive pulmonary disease (COPD) treatment suggest stratifying patients by their symptoms, utilising three main drug classes, but it is unclear if this approach will substantially alter the progression of the disease in the long term. More treatment options are needed which target the underlying pathology of the condition. Whilst many inflammatory cells are implicated in COPD, the neutrophil is by far the most abundant and has been extensively associated with disease pathogenesis. Neutrophil products are thought to be key mediators of inflammatory changes in the airways of COPD patients, causing pathological features such as emphysema and hypersecretion of mucus. High rates of bacterial colonisation and recurrent infective exacerbations of COPD, as well as evidence of neutrophil-associated host damage suggest that neutrophil functions may be impaired in COPD. This concept is supported by studies demonstrating impaired migratory accuracy and increased degranulation and reactive oxygen species release, with some evidence of altered cellular signalling pathways which might be exploitable as therapeutic targets. This review discusses our evolving understanding of neutrophil function in both health and COPD and highlights the role of this cell in disease pathogenesis, to determine whether this key inflammatory mediator represents a viable therapeutic target to prevent disease progression.

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“…While NETs are favorable in the host defense against pathogens, secondary damage to tissue from sustained formation can lead to a cascade of inflammatory reactions, resulting in organ damage, cancer, tissue loss and thrombosis. When dysregulated, excessive NET release has been implicated in diseases, including lupus 10 , COPD 11 , type 2 diabetes 12 , chronic inflammation 13 , cystic fibrosis 14 , autoimmunity 15 , and cancers 16 , among others 17,18 .…”

Section: Introductionmentioning

confidence: 99%

Netome: The Molecular Characterization of Neutrophil Extracellular Traps (NETs)

Scieszka

Lin

et al. 2020

Preprint

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Neutrophils are the most abundant type of white blood cells in humans with biological roles relevant to inflammation and fighting infections. The release of neutrophil extracellular DNA aims to control invasion by bacteria, viruses, fungi, and tissue damage. Neutrophil Extracellular Traps (NETs) act as antimicrobial agents triggering immune signaling through the release of the nuclear content into the extracellular space. Although intense investigations have elucidated the pathways preceding NET formation, the exact molecular composition of released NETs has not been mapped. We aimed to decode the sequences of DNA and proteins from NETs. With emerging needs to understand neutrophil functions precisely, we open the field of NETOMIC studies through isolation of NETs in combination with omics approaches including shotgun genomics and proteomics. Our in vitro NET isolation methodology allowed for unprecedented replicability with induction in a sterile inflammation model system. Enrichment of mitochondrial DNA and telomere sequences are significantly expressed in NET genomes. This study revealed that the genomic sequence released in the extracellular milieu is not stochastically serving as a scaffold for a repertoire of proteins involved in neutrophil protective functions. Collectively, we established the gene and protein signatures exclusive to the extracellular NETs in comparison to undifferentiated and differentiated neutrophil states, further guiding future detection of specific regions needed for diagnostics and targeted therapies of NET related conditions.

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Neutrophil extracellular traps (NETs) in COPD: A potential novel mechanism for host damage in acute exacerbations

Cited by 11 publications

References 0 publications

Understanding the role of neutrophils in chronic inflammatory airway disease

Understanding the role of neutrophils in chronic inflammatory airway disease

Neutrophilic Inflammation in the Pathogenesis of Chronic Obstructive Pulmonary Disease

Netome: The Molecular Characterization of Neutrophil Extracellular Traps (NETs)

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