Abstract
Eosinophil extracellular traps (EETs), a complex of DNA fibers and cytotoxic granule proteins, are implicated in the development of asthma; however, the pathophysiological function of EETs in immune responses has not been fully determined. The present study investigated the characteristics of EETs from patients with non-severe asthma (NSA, n = 20) and severe eosinophilic asthma (SEA, n = 20) and evaluated EET function. The percentage of EET-forming peripheral blood eosinophils stimulated with IL-5 and LPS was significantly higher in patients with SEA than in those with NSA (P = 0.009). This percentage negatively correlated with baseline FEV1 (r = −0.350, P = 0.027) and positively correlated with serum eosinophil-derived neurotoxin levels in asthmatic subjects (r = 0.437, P = 0.018). In addition, EET formation was markedly associated with reactive oxygen species production (r = 0.750, P < 0.001). These EETs exhibited an autocrine function to induce eosinophil degranulation, which led to granule protein production. Airway epithelial cells stimulated with EETs exhibited increased epithelial detachment and permeability and pro-inflammatory cytokine release. However, EETs were not significantly associated with mast cell activation. The present study suggests that peripheral blood eosinophils from patients with SEA may be more activated to produce EETs than those from patients with NSA, which further induces inflammation in asthmatic airways. Therefore, regulation of EET formation and function may be a novel therapeutic approach for asthma management.
Highlights
Asthma is a complicated airway disease with bronchial hyperresponsiveness[1]
Unstimulated eosinophils exhibited no significant differences between the 2 groups (Fig. 1b), which indicates that eosinophils from patients with severe eosinophilic asthma (SEA) may be more activated to produce extracellular traps (EETs)
Eosinophils from patients with SEA were more activated than eosinophils from patients with non-severe asthma (NSA), which increased reactive oxygen species (ROS) production and EET formation
Summary
Asthma is a complicated airway disease with bronchial hyperresponsiveness[1]. The disease exists worldwide in a broad spectrum of phenotypes, and 300 million people are affected. ~10% of asthmatic patients with severe symptoms are poorly controlled with conventional treatment[2,3]. These patients experience frequent asthma exacerbations with morbidity/mortality and consume more healthcare resources, which results in hospital admissions and work loss[4]. Eosinophils play an important role in innate immunity during parasitic and helminthic infections[7]. Whether these cells are beneficial in asthma is not certain because substantial evidence has demonstrated a role for eosinophils in tissue damage and asthma symptoms[8]. High levels of granule proteins are indicative of eosinophil activation and degranulation, which is associated with SEA
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