The Composition of Tracheobronchial Secretions in Cystic Fibrosis

Chernick, Warren S.; Reid, Lynne

doi:10.1136/pgmj.37.432.596

Cited by 45 publications

(54 citation statements)

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“…Previous studies of DNA, F-actin [43], alginate [44], and other anionic filaments present at sites of infection confirm the generality of these biophysical arguments and suggest strategies for design of cationic amphiphiles with reduced binding to linear polyelectrolytes without loss of targeting to bacterial surfaces [45]. Even strong inhibition of cationic antibacterial peptide activity by DNA, F-actin, Medical Studies/Studia Medyczne 2017; 33/2 or other natural negatively charged biopolymers was observed in vitro [1][2][3][4][5][6]; their interaction with NETs is much more complex within in vivo settings. Some reports suggest that DNA release from neutrophils represents an innate immune response to trap, maintain, and buffer the release of cationic defence molecules in exact time-space where the pathogens are trapped.…”

Section: Condensation Of Dna By Cationic Peptidesmentioning

confidence: 77%

“…Nevertheless, under physiological settings, excess of biopolymers is eliminated during phagocytosis of cell fragments [1][2][3][4][5][6]. During the inflammation or infectious exposure, chemotactic migration of neutrophils towards infected/inflamed tissue results in accumulation of PE in the extracellular fluid both as the consequence of formation of neutrophil extracellular traps (NETs) and activity of neutrophil proteases.…”

Section: Dna and F-actin Accumulation In Extracellular Compartmentmentioning

confidence: 99%

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Neutrophil extracellular traps as the main source of eDNA

Cieśluk¹,

Piktel²,

Wątek³

et al. 2017

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Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed DNA together with accompanying proteins, including histones and antimicrobial peptides released from activated neutrophils as part of the first-line defence against pathogens. Despite the protective role of neutrophils, a number of studies indicate that overproduction of NETs followed by accumulation of extracellular DNA (eDNA) and other negatively-charged polyelectrolytes (PE) such as F-actin, contribute to the pathogenesis of some diseases. Neutrophil extracellular traps are also recognised as the structural and functional support of microbial biofilms and should thus be considered as therapeutic targets. Importantly, the chemical nature of PE permits aggregate formation induced by a number of polycations occurring naturally in the human body, including cationic antimicrobial peptides. This review summarises recent reports focused on the clinical significance of NET-derived eDNA and PE and discusses the potential therapeutic strategies to limit the negative consequences of eDNA accumulation.

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Section: Condensation Of Dna By Cationic Peptidesmentioning

confidence: 77%

Section: Dna and F-actin Accumulation In Extracellular Compartmentmentioning

confidence: 99%

Neutrophil extracellular traps as the main source of eDNA

Cieśluk¹,

Piktel²,

Wątek³

et al. 2017

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“…The exact reason for this positive effect remains unclear. CF is characterized by an abnormal rheology of the mucus layer [23,24], due to the presence of an increased amount of DNA, originating especially from neutrophils [7,8]. The effect of rhDNAse is based on depolymerization of this DNA [25].…”

Section: Discussionmentioning

confidence: 99%

“…Mucociliary clearance of the viscous mucus is impaired, which causes an ideal basis for colonization and infection with microorganisms. These infections give local inflammation with an influx of predominantly neutrophils [7,8]. Degradation of these neutrophils causes DNA release, which leads to an increase in viscosity of sputum, further increasing the susceptibility for colonization and infection [9].…”

Section: Introductionmentioning

confidence: 99%

No positive effect of rhdnase on the pulmonary colonization in children with cystic fibrosis

Bonestroo

Slieker

Arets

2016

Monaldi Arch Chest Dis

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Background. Long-term clinical trials have shown that daily treatment with recombinant human deoxyribonuclease (rhDNAse) in patients with mild to moderate cystic fibrosis (CF) improves lung function and decreases the number of respiratory exacerbations. The aim of this study was to analyze the effect of rhDNAse on the bacterial colonization of the airways in children with CF. Methods. This was a retrospective cohort study. From the database of the CF Center Utrecht, we selected two groups, an rhDNAse group (daily 2.5 mg rhDNAse) and a control group (no rhDNAse). Primary outcome parameter was the difference in change in bacterial colonization between the treatment and control group during 1.5-year. Secondary outcome parameters were changes in lung function (FEV1) and pulmonary exacerbations. Results. Children treated with rhDNAse showed no significant changes in bacterial colonization during the treatment period, apart from an increase of P. aeruginosa positive cultures, both compared to baseline (53.1% versus 25%, p<0.05) and control group (no change during study period, 37% versus 37%). The change in FEV1 after one year of treatment was +4.0% in the treatment group versus -0.3% in the control group (p=0.22). There were no significant changes in number of pulmonary exacerbations. Conclusions. This study showed no significant beneficial decrease in bacterial airway colonization during 1.5-year of treatment with rhDNAse. The positive effects of rhDNAse on the lung function can therefore not be explained by a change in airway colonization.

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“…Airway secretion purulence is generally associated with an increased DNA content and increased viscosity [7]. Nevertheless, some controversy exists in the literature on the specific role of DNA.…”

mentioning

confidence: 99%

Effects of rhDNase on purulent airway secretions in chronic bronchitis

Puchelle

Zahm²,

Bentzmann³

et al. 1996

European Respiratory Journal

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ABSTRACT. Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce in vitro the viscosity and to improve the transport capacity of purulent respiratory mucus in cystic fibrosis. During episodes of exacerbation of chronic bronchitis, the patients generally expectorate purulent mucus. Purulence of mucus is associated with an increased deoxyriboneucleic acid (DNA) concentration.We analyzed in vitro the potential effect of rhDNase on chronic bronchitis mucus transport by the ciliary activity (frog palate model) and by simulated cough (cough machine model), as well as the effect on mucus viscosity (controlled stress rheometer) and surface properties (contact angle). Purulent sputa collected from patients with chronic bronchitis (n=15) during an episode of exacerbation were incubated for 30 min at 37°C with either rhDNase at two different concentrations (final concentration 2 or 4 µg·mL -1 ) or placebo.The These findings demonstrate that recombinant deoxyribonuclease may exert a beneficial effect on mucus clearance in vitro by altering the viscosity and surface properties of the purulent chronic bronchitic sputum samples.

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The Composition of Tracheobronchial Secretions in Cystic Fibrosis

Cited by 45 publications

References 1 publication

Neutrophil extracellular traps as the main source of eDNA

Neutrophil extracellular traps as the main source of eDNA

No positive effect of rhdnase on the pulmonary colonization in children with cystic fibrosis

Effects of rhDNase on purulent airway secretions in chronic bronchitis

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