Neutrophil Extracellular Traps in Asthma: Friends or Foes?

Abstract

Asthma is a chronic inflammatory disease characterized by variable airflow limitation and airway hyperresponsiveness. A plethora of immune and structural cells are involved in asthma pathogenesis. The roles of neutrophils and their mediators in different asthma phenotypes are largely unknown. Neutrophil extracellular traps (NETs) are net-like structures composed of DNA scaffolds, histones and granular proteins released by activated neutrophils. NETs were originally described as a process to entrap and kill a variety of microorganisms. NET formation can be achieved through a cell-death process, termed NETosis, or in association with the release of DNA from viable neutrophils. NETs can also promote the resolution of inflammation by degrading cytokines and chemokines. NETs have been implicated in the pathogenesis of various non-infectious conditions, including autoimmunity, cancer and even allergic disorders. Putative surrogate NET biomarkers (e.g., double-strand DNA (dsDNA), myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (CitH3)) have been found in different sites/fluids of patients with asthma. Targeting NETs has been proposed as a therapeutic strategy in several diseases. However, different NETs and NET components may have alternate, even opposite, consequences on inflammation. Here we review recent findings emphasizing the pathogenic and therapeutic potential of NETs in asthma.

Granular Insights: Neutrophil Predominance and Elastase Release in Severe Asthma Exacerbations in a Pediatric Cohort

“…Our assay for the quantification of extracellular elastase would not distinguish between secreted elastase, i.e., regulated exocytosis, and the extrusion in neutrophil-extracellular traps or NETs. Recently, there has been more interest in the role of NETs in the pathogenesis of asthma [ 33 ]. The role of NETs in pathogen killing is clearly necessary in some asthma exacerbations, but NETs can also be induced in viral settings, including in response to rhinovirus and influenza [ 34 , 35 ], common triggers for asthma exacerbation in children.…”

Metabolic Inflammation and Cellular Immunity

“…Among the eminent review papers published in this Special Issue, Poto and colleagues reviewed the pathogenic as well as therapeutic potential of neutrophil extracellular traps (NETs: net-like structures composed of DNA scaffolds, histones and granular proteins released by activated neutrophils) in asthma, which is consistent with their deleterious roles in autoimmunity, cancer, and allergy as well as beneficial effects via NETosis and resolution of inflammation by degrading cytokines/chemokines. The authors also elucidated putative surrogate NET biomarkers in this study [ 15 ].…”