Biological function of eosinophil extracellular traps in patients with severe eosinophilic asthma

• Published in: Experimental & molecular medicine 2018, 50(0), , pp.1-8
• Main Authors: Choi, Youngwoo, Le Pham, Duy, Lee, Dong-Hyun, Lee, So-Hee, Kim, Seung-Hyun, Park, Hae-Sim
• Format: Article
• Language: English
• Subjects: 13/106; 14/19; 631/250/1933; 631/250/256; Asthma; Asthma - blood; Asthma - immunology; Asthma - metabolism; Asthma - pathology; Autocrine Communication; Autocrine signalling; Biomedical and Life Sciences; Biomedicine; Cell activation; Cell Line; Cytotoxicity; Degranulation; Deoxyribonucleic acid; DNA; Eosinophil-derived neurotoxin; Eosinophils - immunology; Eosinophils - metabolism; Eosinophils - pathology; Epithelial cells; Epithelial Cells - immunology; Epithelial Cells - pathology; Extracellular Traps - metabolism; Female; Humans; Immune response; Inflammation; Interleukin 5; Leukocytes (eosinophilic); Lipopolysaccharides; Lung - pathology; Male; Mast Cells - metabolism; Medical Biochemistry; Middle Aged; Molecular Medicine; Peripheral blood; Permeability; Reactive oxygen species; Reactive Oxygen Species - metabolism; Respiratory tract; Stem Cells; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-018-0136-8

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 FEV 1 ( 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. Asthma: Traps to target for treatment Controlling the formation of mesh-like structures of DNA and protein which induce airway damage in asthma could offer new therapeutic opportunities, especially for patients who do not respond well to conventional treatments. The structures are produced by activated cells as part of the immune response in asthma. They are known as eosinophil extracellular traps (EETs) since they are most prominently released by the activity of white blood cells called eosinophils. Hae-Sim Park and colleagues at Ajou University in South Korea studied the involvement of EETs in patients with severe asthma. Their results suggest eosinophils are more activated to create damaging EETs in patients with severe asthma than in those with less severe forms of the disease. Searching for ways to control EET formation could be a fruitful approach to helping patients with severe eosinophilic as