<i>Pseudomonas aeruginosa</i>
            triggers CFTR-mediated airway surface liquid secretion in swine trachea

Luan, Xiaojie; Campanucci, Verónica A.; Nair, Manoj; Yılmaz, Orhan; Belev, George; Machen, Terry E.; Chapman, Dean; Ianowski, Juan P.

doi:10.1073/pnas.1406414111

Cited by 26 publications

(41 citation statements)

References 45 publications

(68 reference statements)

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“…The technique exploits the large difference in x-ray refractive index between the air and the ASL layer, which generates a strong signal at the air/ASL interface under x-ray phase contrast imaging (PCI) (Fig. 1b ) 18 , 19 . Because PCI does not allow us to observe the ASL/tissue interface, we used agarose beads instilled into the swine airway as ‘measuring rods’ to measure the ASL height by determining the position of the tissue with respect to the air/ASL interface (Fig.…”

Section: Resultsmentioning

confidence: 99%

Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens

et al. 2017

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Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel, which can result in chronic lung disease. The sequence of events leading to lung disease is not fully understood but recent data show that the critical pathogenic event is the loss of the ability to clear bacteria due to abnormal airway surface liquid secretion (ASL). However, whether the inhalation of bacteria triggers ASL secretion and whether this is abnormal in cystic fibrosis has never been tested. Here we show, using a novel synchrotron-based in vivo imaging technique, that wild-type pigs display both a basal and a Toll-like receptor-mediated ASL secretory response to the inhalation of cystic fibrosis relevant bacteria. Both mechanisms fail in CFTR−/− swine, suggesting that cystic fibrosis airways do not respond to inhaled pathogens, thus favoring infection and inflammation that may eventually lead to tissue remodeling and respiratory disease.

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Section: Resultsmentioning

confidence: 99%

Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens

et al. 2017

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“…PA LPS has also been shown to generate reactive oxygen species (ROS) via the PKC-NADPH oxidase signaling pathway in epithelial cells, which leads to up-regulation of MUC5AC transcription (Li et al, 2013; Yan et al, 2008). The induction of CFTR-dependent airway surface liquid secretion following exposure to bacteria has also been observed in swine tracheal explants (Luan et al, 2014). It is hypothesized that PA may be responsible, via these modes of actions described, for the excessive mucus production seen in CF patients, rather than the CF lung environment itself.…”

Section: Respiratory Tract Mucusmentioning

confidence: 92%

The Interaction between Respiratory Pathogens and Mucus

Zanin

Baviskar

Webster

et al. 2016

Cell Host & Microbe

245

228

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Summary The interaction between respiratory pathogens and their hosts is complex and incompletely understood. This is particularly true when pathogens encounter the mucus layer covering the respiratory tract. The mucus layer provides an essential first host barrier to inhaled pathogens that can prevent pathogen invasion and subsequent infection. Respiratory mucus has numerous functions and interactions, both with the host and with pathogens. This review summarizes the current understanding of respiratory mucus and its interactions with the respiratory pathogens Pseudomonas aeruginosa, respiratory syncytial virus and influenza viruses, with particular focus on influenza virus transmissibility and host-range specificity. Based on current findings we propose that respiratory mucus represents an understudied host-restriction factor for influenza virus.

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“…It stimulated gland secretion. Beads coated with S. aureus and H. influenzae also induced CFTR-dependent increases in ASL depth (401).…”

Section: Nonneural Endogenous Agentsmentioning

confidence: 92%

Airway Gland Structure and Function

Widdicombe

Wine

2015

Physiological Reviews

177

221

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Submucosal glands contribute to airway surface liquid (ASL), a film that protects all airway surfaces. Glandular mucus comprises electrolytes, water, the gel-forming mucin MUC5B, and hundreds of different proteins with diverse protective functions. Gland volume per unit area of mucosal surface correlates positively with impaction rate of inhaled particles. In human main bronchi, the volume of the glands is ∼ 50 times that of surface goblet cells, but the glands diminish in size and frequency distally. ASL and its trapped particles are removed from the airways by mucociliary transport. Airway glands have a tubuloacinar structure, with a single terminal duct, a nonciliated collecting duct, then branching secretory tubules lined with mucous cells and ending in serous acini. They allow for a massive increase in numbers of mucus-producing cells without replacing surface ciliated cells. Active secretion of Cl(-) and HCO3 (-) by serous cells produces most of the fluid of gland secretions. Glands are densely innervated by tonically active, mutually excitatory airway intrinsic neurons. Most gland mucus is secreted constitutively in vivo, with large, transient increases produced by emergency reflex drive from the vagus. Elevations of [cAMP]i and [Ca(2+)]i coordinate electrolyte and macromolecular secretion and probably occur together for baseline activity in vivo, with cholinergic elevation of [Ca(2+)]i being mainly responsive for transient increases in secretion. Altered submucosal gland function contributes to the pathology of all obstructive diseases, but is an early stage of pathogenesis only in cystic fibrosis.

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Pseudomonas aeruginosa triggers CFTR-mediated airway surface liquid secretion in swine trachea

Cited by 26 publications

References 45 publications

Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens

Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens

The Interaction between Respiratory Pathogens and Mucus

Airway Gland Structure and Function

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