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

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?

SUBMITTER: Choi Y

PROVIDER: S-EPMC6095846 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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

Choi Youngwoo Y Le Pham Duy D Lee Dong-Hyun DH Lee So-Hee SH Kim Seung-Hyun SH Park Hae-Sim HS

Experimental & molecular medicine 20180816 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 ...[more]

PMID: 30115903

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Project description:BackgroundEndogenous DNA derived from nuclei or mitochondria is released into the blood circulation as cell-free DNA (cfDNA) following cell damage or death. cfDNA is associated with various pathological conditions; however, its clinical significance in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unclear. This study aimed to evaluate the clinical significance of cfDNA in AAV.MethodsWe enrolled 35 patients with AAV, including 10 with eosinophilic granulomatosis with polyangiitis (EGPA), 13 with microscopic polyangiitis, and 12 with granulomatosis with polyangiitis. Serum cf-nuclear DNA (cf-nDNA) and cf-mitochondrial DNA (cf-mtDNA) levels were measured by quantitative polymerase chain reaction before and after the initiation of immunosuppressive therapy. Tissue samples from EGPA patients were examined by immunofluorescence and transmission electron microscopy. The structure of eosinophil extracellular traps (EETs) and neutrophil extracellular traps (NETs) and stability against DNase were assessed in vitro. Platelet adhesion of EETs were also assessed.ResultsSerum cf-nDNA and cf-mtDNA levels were significantly higher in AAV than in healthy controls, with the highest levels in EGPA; however, serum DNase activities were comparable among all groups. cf-nDNA and cf-mtDNA decreased after treatment and were associated with disease activity only in EGPA. Blood eosinophil count and plasma D-dimer levels were significantly correlated with cf-nDNA in EGPA and cf-mtDNA. EGPA tissue samples showed lytic eosinophils and EETs in small-vessel thrombi. The structure of EETs showed bolder net-like chromatin threads in vitro and EETs showed greater stability against DNase than NETs. EETs provided a scaffold for platelet adhesion.ConclusioncfDNA was increased in EGPA, associated with disease activity. The presence of DNase-resistant EETs in small-vessel thrombi might contribute to higher concentration of cfDNA and the occurrence of immunothrombosis in EGPA.

Dataset Information

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

Publications

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

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