MINI-SYMPOSIUM: MUCUSAirway mucus in cystic fibrosis
Section snippets
INTRODUCTION
Defective expression and function of the cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis (CF) airway epithelial cells are associated with mucus hypersecretion, inflammation and infection that begin early in life and lead to a persistent vicious cycle with marked airway obstruction and infection responsible for the morbidity and mortality in patients with CF.
Although thick and adhesive airway mucus represents a hallmark of the disease in CF patients at an advanced
Ion and water composition of CF airway mucus: effect on mucociliary transport
The mucus covering the airway mucociliary epithelium is generally described as a biphasic layer composed of a periciliary sol layer in which the cilia beat and a more superficial gel layer which constitutes an efficient barrier against micro-organisms.
The hydration of the periciliary fluid layer under homeostatic conditions is mainly regulated by luminal/basolateral water transport coupled to active transepithelial Na+ transport. The accompanying absorptive movement of Cl− and water occurs
RHEOLOGICAL PROPERTIES OF CF AIRWAY MUCUS AND RELATED ABNORMAL MUCOCILIARY AND COUGH TRANSPORT PROPERTIES
The airway mucus is a very complex biological fluid that is characterised by flow (viscosity) and deformation (viscoelastic) properties as well as surface properties that are independent of the viscoelastic properties and control the capacity of airway mucus to protect and lubricate the airway mucosa. In CF, there are no data demonstrating that the native airway mucus is hyperviscous. In human bronchial airway xenograft, the viscosity of airway fluid inside the lumen of the human CF tracheal
IN VIVO MODELS FOR STUDYING CF AIRWAY MUCUS
Most of the studies of CF airway mucus have been carried out on expectorated sputum at a stage of the disease where hypersecretion is already present. It is much more difficult to collect the airway mucus at an early stage of the disease and to compare the results with that obtained in healthy control subjects, due to the small volume of secreted mucus. To collect “normal” airway mucus and determine the ASL composition in intact normal and CF airways, very small samples were collected using
RESEARCH DIRECTIONS
- •
Develop non-invasive and in vivo techniques to identify early airway mucus disorders in CF.
- •
Identify the nature of antibacterial factors impaired in CF airway mucus.
- •
Define the role of bacteria (Staphylococcus aureus and Haemophilus influenzae) and viruses identified early in CF, in airway mucus disorders.
- •
Better define the relationship between CFTR dysfunction and CF airway mucus disorders.
- •
Develop strategies focusing on CF airway mucus disorders.
PRACTICE POINTS
- •
There are no data to support the hypothesis that uninfected mucus in the newborn with cystic fibrosis has abnormal viscosity or elasticity.
- •
Cystic fibrosis airways have an increased propensity to inflammation that may occur in the absence of overt infection. Furthermore the risk of infection is increased by the inactivation of one or more antimicrobial peptides as well as the development of abnormal mucus properties.
- •
In purulent secretions (sputum), the DNA/F-actin polymer network and alterations
Acknowledgements
We would like to thank the “Association Vaincre la Mucoviscidose” for support in the research work that has been conducted in our laboratory.
References (36)
- et al.
Bidirectional transepithelial water transport: measurement and governing mechanisms
Biophys. J.
(1999) - et al.
Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid
Cell
(1996) - et al.
The CF salt controversy: in vivo observations and therapeutic approaches
Mol. Cell
(2001) - et al.
Relationships between the lipid content and the rheological properties of airway secretions in cystic fibrosis
Clin. Chim. Acta
(1987) The genesis of cystic fibrosis lung disease
J. Clin. Invest.
(1999)- et al.
CFTR involvement in chloride, bicarbonate and liquid secretion by airway submucosal glands
Am. J. Physiol.
(1999) - et al.
Osmotic water permeabilities of cultured, well-differentiated normal and cystic fibrosis airway epithelia
J. Clin. Invest.
(2000) - et al.
Na+ transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation
J. Clin. Invest.
(1986) Lung disease in cystic fibrosis: is airway surface liquid composition abnormal?
Am. J. Physiol. Lung Cell Mol. Physiol.
(2001)- et al.
X-ray microanalysis of airway surface liquid collected in cystic fibrosis mice
Am. J. Physiol. Lung Cell Mol. Physiol.
(2001)
Early alterations in airway mucociliary clearance and inflammation of the lamina propria in CF mice
Am. J. Physiol.
Overproduction of the CFTR R domain leads to increased levels of asialoGM1 and increased Pseudomonas aeruginosa binding by epithelial cells
Am. J. Respir. Cell Mol. Biol.
Modulation of host-bacterial interactions by collectins
Am. J. Respir. Cell Mol. Biol.
Augmentation of innate host defence by expression of a cathelicidin antimicrobial peptide
Infect. Immun.
Mouse beta-defensin 1 is a salt-sensitive antimicrobial peptide present in epithelia of the lung and urogenital tract
Infect. Immun.
Salt-independent abnormality of antimicrobial activity in cystic fibrosis airway surface fluid
Am. J. Respir. Cell Mol. Biol.
Chinks in the armor of the airway
Am. J. Respir. Cell Mol. Biol.
Abnormal glutathione transport in cystic fibrosis airway epithelia
Am. J. Physiol. Lung Cell Mol. Physiol.
Cited by (67)
Nicotinic acetylcholine receptor subtype expression, function, and pharmacology: Therapeutic potential of α-conotoxins
2023, Pharmacological ResearchCystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond
2023, European Respiratory JournalComparison between different internal cross-sections for pulmonary secretion suction catheters
2022, Research on Biomedical Engineering