Dataset Information

Plasma neutrophil extracellular trap level is modified by disease severity and inhaled corticosteroids in chronic inflammatory lung diseases.

ABSTRACT: A flow cytometry-based method was developed to quantify in vivo circulating neutrophil extracellular trap (NET) levels in plasma and compare them in patients with different chronic inflammatory lung diseases. Seventeen asthmatic and 11 control children, 12 adult controls, 46 asthmatic, 6 COPD and 6 adult patients with asthma-COPD overlap syndrome (ACOS) were recruited in the study. The presence of NETs in unstimulated cell-free plasma was confirmed and visualized by confocal laser-scanning microscopy. No significant differences were found in plasma NET levels between children and adults, children with or without asthma and adults with or without asthma, COPD or ACOS. When asthmatic patients were stratified according to their disease severity the average plasma NET level was significantly higher in asthmatic patients with more serious symptoms (adjusted p?=?0.027). Patients with poorer pulmonary functions had higher plasma NET levels which negatively correlated with the FEV1 values (r?=?-0.39, p?=?0.002). Patients who were medicated daily with inhaled corticosteroids (ICS) had significantly lower average plasma NET level than patients who did not or just occasionally used ICS (p?=?0.027). If further studies confirm the NET-lowering effect of ICS in the circulation, it can be utilized in diseases where NETosis contributes to the pathogenesis.

SUBMITTER: Gal Z

PROVIDER: S-EPMC7062787 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Plasma neutrophil extracellular trap level is modified by disease severity and inhaled corticosteroids in chronic inflammatory lung diseases.

Gál Zsófia Z Gézsi András A Pállinger Éva É Visnovitz Tamás T Nagy Adrienne A Kiss András A Sultész Monika M Csoma Zsuzsanna Z Tamási Lilla L Gálffy Gabriella G Szalai Csaba C

Scientific reports 20200309 1

A flow cytometry-based method was developed to quantify in vivo circulating neutrophil extracellular trap (NET) levels in plasma and compare them in patients with different chronic inflammatory lung diseases. Seventeen asthmatic and 11 control children, 12 adult controls, 46 asthmatic, 6 COPD and 6 adult patients with asthma-COPD overlap syndrome (ACOS) were recruited in the study. The presence of NETs in unstimulated cell-free plasma was confirmed and visualized by confocal laser-scanning micro ...[more]

PMID: 32152402

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Project description:Neutrophils undergo a unique form of cell death to generate neutrophil extracellular traps (NETs). It is well established that citrullination of histones (e.g., CitH3) facilitates chromatin decondensation during NET formation (NETosis), particularly during calcium-induced NETosis that is independent of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activation. However, the importance of other forms of histone modifications in NETosis has not been established. We considered that acetylation of histones would also facilitate NETosis. To test this hypothesis, we induced NOX-dependent NETosis in human neutrophils with phorbol myristate acetate or lipopolysaccharide (from Escherichia coli 0128), and NOX-independent NETosis with calcium ionophores A23187 or ionomycin (from Streptomyces conglobatus) in the presence or absence of two pan histone deacetylase inhibitors (HDACis), belinostat and panobinostat (within their half maximal inhibitory concentration (IC50) range). The presence of these inhibitors increased histone acetylation (e.g., AcH4) in neutrophils. Histone acetylation was sufficient to cause a significant increase (~20%) in NETosis in resting neutrophils above baseline values. When acetylation was promoted during NOX-dependent or -independent NETosis, the degree of NETosis additively increased (~15?30%). Reactive oxygen species (ROS) production is essential for baseline NETosis (mediated either by NOX or mitochondria); however, HDACis did not promote ROS production. The chromatin decondensation step requires promoter melting and transcriptional firing in both types of NETosis; consistent with this point, suppression of transcription prevented the NETosis induced by the acetylation of histones. Collectively, this study establishes that histone acetylation (e.g., AcH4) promotes NETosis at baseline, and when induced by both NOX-dependent or -independent pathway agonists, in human neutrophils. Therefore, we propose that acetylation of histone is a key component of NETosis.

Dataset Information

Plasma neutrophil extracellular trap level is modified by disease severity and inhaled corticosteroids in chronic inflammatory lung diseases.

Publications

Plasma neutrophil extracellular trap level is modified by disease severity and inhaled corticosteroids in chronic inflammatory lung diseases.

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