Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Biological function of eosinophil extracellular traps in patients with severe eosinophilic asthma

  • Choi, Youngwoo (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Pham, Duy Le (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Lee, Dong-Hyun (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Lee, So-Hee (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Kim, Seung-Hyun (Clinical Trial Center, Ajou University Medical Center) ;
  • Park, Hae-Sim (Department of Allergy and Clinical Immunology, Ajou University School of Medicine)
  • Received : 2018.03.21
  • Accepted : 2018.05.28
  • Published : 2018.08.31
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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 $FEV_1$ (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.

Keywords

Acknowledgement

Supported by : Ministry of Health & Welfare

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