Structure and Function of the Mucus Clearance System of the Lung

Button, Brenda; Button, Brian

doi:10.1101/cshperspect.a009720

Cited by 67 publications

(64 citation statements)

References 106 publications

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“…AMP) and ecto-5 0nucleotidase (eNT: AMP ! adenosine) (Burch & Picher, 2006;Button & Button, 2013;Picher et al, 2003Picher et al, , 2004Robson et al, 2006). Currently, relatively little is known about the direct role of extracellular AMP in inflammation, except as an intermediate metabolite.…”

Section: Discussionmentioning

confidence: 95%

Adenosine monophosphate is elevated in the bronchoalveolar lavage fluid of mice with acute respiratory toxicity induced by nanoparticles with high surface hydrophobicity

Dailey¹,

Hernández-Prieto²,

Casas-Ferreira³

et al. 2014

Nanotoxicology

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Inhaled nanomaterials present a challenge to traditional methods and understanding of respiratory toxicology. In this study, a non-targeted metabolomics approach was used to investigate relationships between nanoparticle hydrophobicity, inflammatory outcomes and the metabolic fingerprint in bronchoalveolar fluid. Measures of acute lung toxicity were assessed following single-dose intratracheal administration of nanoparticles with varying surface hydrophobicity (i.e. pegylated lipid nanocapsules, polyvinyl acetate nanoparticles and polystyrene beads; listed in order of increasing hydrophobicity). Broncho-alveolar lavage (BAL) fluid was collected from mice exposed to nanoparticles at a surface area dose of 220 cm(2) and metabolite fingerprints were acquired via ultra pressure liquid chromatography-mass spectrometry-based metabolomics. Particles with high surface hydrophobicity were pro-inflammatory. Multivariate analysis of the resultant small molecule fingerprints revealed clear discrimination between the vehicle control and polystyrene beads (p < 0.05), as well as between nanoparticles of different surface hydrophobicity (p < 0.0001). Further investigation of the metabolic fingerprints revealed that adenosine monophosphate (AMP) concentration in BAL correlated with neutrophilia (p < 0.01), CXCL1 levels (p < 0.05) and nanoparticle surface hydrophobicity (p < 0.001). Our results suggest that extracellular AMP is an intermediary metabolite involved in adenine nucleotide-regulated neutrophilic inflammation as well as tissue damage, and could potentially be used to monitor nanoparticle-induced responses in the lung following pulmonary administration.

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Section: Discussionmentioning

confidence: 95%

Adenosine monophosphate is elevated in the bronchoalveolar lavage fluid of mice with acute respiratory toxicity induced by nanoparticles with high surface hydrophobicity

Dailey¹,

Hernández-Prieto²,

Casas-Ferreira³

et al. 2014

Nanotoxicology

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“…Surface mucus thus becomes more adherent and difficult to clear, rendering cystic fibrosis patients to be considerably more susceptible to recurrent infections [5]. Similarly, the sinonasal surface epithelium is maintained optimally hydrated through CFTR anion channel which regulates the amount of Cl -that is secreted, maintaining an adequate salt content and therefore water which impacts directly on the viscosity of the ASL [6,10]. In order for mucus to be cleared optimally, the PCL needs to reach the height of the outspread cilia, this height being approximately 7-10 µm [4].…”

Section: Asl Homeostasismentioning

confidence: 99%

“…This leads to the formation of excess viscous mucus that adheres to the airway surface and creates a setting that is ideal for recurrent bacterial overgrowth that has the potential to elicit inflammation and cause damage to the surface epithelium [6,7]. This manuscript investigates an alternative therapeutic approach to RS, which would reduce the associated inflammation by improving the MCC thereby allowing ASL to perform its protective functions optimally.…”

Section: Introductionmentioning

confidence: 99%

The Role of Airway Surface Liquid in the Primary Management of Rhinosinusitis

Hendrik¹,

Raubenheimer²

2013

J Interdiscipl Med Dent Sci

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Airway surface liquid forms part of the innate defence mechanism of the respiratory system, including the nasal and paranasal sinuses. Successful mucociliary clearance, which lies at the centre of this defence mechanism, involves the synchronized function of two structures, namely, the periciliary liquid layer and the mucus layer. The two structures have collectively been termed the 'two phase airway surface liquid' system. This system is kept hydrated through regulation of sodium and chloride transport. A well hydrated airway surface liquid that allows the periciliary liquid layer to extend over the height of the outstretched cilia keeping mucus away from the epithelia is considered to be essential for effective mucus clearance and sinonasal health. This mechanism assists in trapping and eliminating foreign particles and, together with antimicrobial peptides, maintains a sterile environment in the nasal and paranasal sinuses, which are continually exposed to microorganisms in the external environment. In diseases such as rhinosinusitis, the mucociliary clearance capacity is diminished; the first line of defence is disrupted allowing for bacterial invasion and infection. This manuscript explores the prospect of an alternative approach for the prophylaxis and primary management of rhinosinusitis based on the maintenance of a well hydrated airway surface liquid.

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“…The drugs are small molecular weight compounds, 51 because proteins do not get across the corneal and conjunctival 52 barriers at adequate quantities [2,3]. 53 After eye drop administration the contact time of the drug on 54 the ocular surface is only a few minutes [4]. The rate of drug elim- 55 ination from the tear fluid is in the range of 0.5-1.0 min À1 , and it 56 has been shown that the drug absorption takes place during the 57 first 2-3 min after instillation [5][6][7].…”

mentioning

confidence: 99%