Role of Neutrophil Extracellular Traps in Asthma and Chronic Obstructive Pulmonary Disease

Abstract

Objective:Asthma and chronic obstructive pulmonary disease (COPD) are representative chronic inflammatory airway diseases responsible for a considerable burden of disease. In this article, we reviewed the relationship between neutrophil extracellular traps (NETs) and chronic inflammatory airway diseases.Data Sources:Articles published up to January 1, 2017, were selected from the PubMed, Ovid Medline, Embase databases, with the keywords of “asthma” or “pulmonary disease, chronic obstructive”, “neutrophils” and “extracellular traps.”Study Selection:Articles were obtained and reviewed to analyze the role of NETs in asthma and COPD.Results:NETs are composed of extracellular DNA, histones, and granular proteins, which are released from activated neutrophils. Multiple studies have indicated that there are a large amount of NETs in the airways of asthmatics and COPD patients. NETs can engulf and kill invading pathogens in the host. However, disordered regulation of NET formation has shown to be involved in the development of asthma and COPD. An overabundance of NETs in the airways or lung tissue could cause varying degrees of damage to lung tissues by inducing the death of human epithelial and endothelial cells, and thus resulting in impairing pulmonary function and accelerating the progress of the disease.Conclusions:Excessive NETs accumulate in the airways of asthmatics and COPD patients. Although NETs play an essential role in the innate immune system against infection, excessive components of NETs can cause lung tissue damage and accelerate disease progression in asthmatics and COPD patients. These findings suggest that administration of NETs could be a novel approach to treat asthma and COPD. Mechanism studies, clinical practice, and strategies to regulate neutrophil activation or directly interrupt NET function in asthmatics and COPD patients are desperately needed.

Plasma neutrophil extracellular trap level is modified by disease severity and inhaled corticosteroids in chronic inflammatory lung diseases

“…In contrast to asthma, patients with chronic obstructive pulmonary disease (COPD) have progressive and generally irreversible airflow obstruction. Disease progression, GOLD (Global Initiative for Chronic Obstructive Lung Disease) status and exacerbations of COPD are connected to neutrophilia in lungs [3][4][5] . Asthma-COPD overlap syndrome (ACOS) is a consensus-based phenotype, not an individual disease.…”

“…In the last decades, it has been discovered that neutrophils beside degranulation and phagocytosis can form neutrophil extracellular traps (NETs) to different triggers which process has been termed NETosis. In vivo, several biological molecules may elicit NETosis including interleukin-8 and tumor necrosis factor-α, both of which have a prominent role in asthma and COPD 3 . In vitro, the pharmacological agent phorbol-12-myristate-13-acetate (PMA) is a known strong inducer of NETosis that is routinely used in studies of NETs.…”

Neutrophil extracellular traps activate lung fibroblast to induce polymyositis‐related interstitial lung diseases via TLR9‐miR‐7‐Smad2 pathway

“…[30][31][32] NETs also involve in the development of inflammation through inducing the release of cytokine by airway epithelial cells. Our experimental data suggested that NETs Increasing evidence has shown that NETs and their components cause damage of endothelial and epithelial cells, thus to impair pulmonary function and accelerate the progress of chronic obstructive pulmonary disease.…”

The cGAS‐STING pathway: The role of self‐DNA sensing in inflammatory lung disease

“…129,130 However, an overabundance of NETs has been implicated in a number of lung diseases, such as CF, COPD, asthma, and acute respiratory distress syndrome. [151][152][153] Whether NETs could serve as a dsDNA source for cGAS-STING signaling activation needs further investigation. Oxidative stress and mitochondrial dysfunction also serve as a potential dsDNA origin in pulmonary disease.…”