Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease.

@article{Verkman2003RoleOA,
  title={Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease.},
  author={Alan S. Verkman and Yuanlin Song and Jay R. Thiagarajah},
  journal={American journal of physiology. Cell physiology},
  year={2003},
  volume={284 1},
  pages={
          C2-15
        }
}
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) protein, an epithelial chloride channel expressed in the airways, pancreas, testis, and other tissues. A central question is how defective CFTR function in CF leads to chronic lung infection and deterioration of lung function. Several mechanisms have been proposed to explain lung disease in CF, including abnormal airway surface liquid (ASL) properties, defective airway submucosal gland function… 

Figures and Tables from this paper

Cystic fibrosis mice rehabilitated for studies of airway gland dysfunction
TLDR
A study of submucosal gland secretion by the mucus droplet approach in the trachea of CFTR–/– mice by Ianowski et al. published in this issue of The Journal of Physiology has broken down the doctrine that CFTR null mice were not a model for studying CFTR dysfunction.
Defective organellar acidification as a cause of cystic fibrosis lung disease: reexamination of a recurring hypothesis.
  • P. Haggie, A. Verkman
  • Biology, Medicine
    American journal of physiology. Lung cellular and molecular physiology
  • 2009
TLDR
It is concluded that biologically significant involvement of CFTR in organellar acidification is unlikely and there is an expanding body of evidence supporting the involvement of non-CFTR chloride channels in organeller acidification.
The role of airway epithelium and blood neutrophils in the inflammatory response in cystic fibrosis.
A small molecule CFTR inhibitor produces cystic fibrosis‐like submucosal gland fluid secretions in normal airways
TLDR
The relatively hyper‐viscous and acidic fluid secretions produced by acute CFTR inhibition support a role for defective gland function in CF lung disease and provide a rational basis for pharmacological creation of a large animal model of CF.
Emerging relationship between CFTR, actin and tight junction organization in cystic fibrosis airway epithelium.
TLDR
The correction of CFTR mutations by either gene or drug therapies, as well as by stem cell-based interventions, can determine the resumption of a physiological organization of actin stress fibers and TJ structure and barrier function, further indicating the close interrelationship among these processes.
Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice
TLDR
It is concluded that increasing airway Na+ absorption initiates cystic fibrosis-like lung disease and produces a model for the study of the pathogenesis and therapy of this disease.
Airway surface dehydration in cystic fibrosis: pathogenesis and therapy.
  • R. Boucher
  • Medicine, Biology
    Annual review of medicine
  • 2007
TLDR
Rehydration therapies may slow the progression of CF lung disease in patients with established bacterial infection and may prevent the onset ofCF lung disease if initiated early in life.
Cystic fibrosis: a disease of vulnerability to airway surface dehydration.
  • R. Boucher
  • Biology, Medicine
    Trends in molecular medicine
  • 2007
Cystic fibrosis and airway submucosal glands
TLDR
The demonstration that the predominant sites of expression of the CF gene in normal lungs are the submucosal glands, together with the histological observations showing that hyperplasia of these glands and mucin occlusion of the gland ducts are the earliest signs of disease in the CF lung, suggest that malfunction of the submunity glands may be an important factor contributing to the early pathophysiology of CF lung disease.
Mucus secretion by single tracheal submucosal glands from normal and cystic fibrosis transmembrane conductance regulator knockout mice
TLDR
A novel defect in local regulation of glands lacking CFTR which may also compromise airway defence in CF patients is revealed.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 104 REFERENCES
Role of CFTR in airway disease.
TLDR
The details of this pathophysiological cascade, whereby the deletion or impairment of CFTR chloride channel function produces lung disease, are provided in the hope that its understanding will promote the development of new therapies for CF.
Regulation and functional significance of airway surface liquid pH.
TLDR
The evidence in support of a lumenal acidification hypothesis in the CF lung is evaluated, current knowledge of pH regulation in the normal airway is summarized and how hyper-acidified airway secretions could contribute to the pathogenesis of CF lung disease is illustrated.
Localization of the cystic fibrosis transmembrane conductance regulator in airway secretory glands.
TLDR
The data suggest that in airway tissues, CFTR could be involved in intracellular processes of the mucus exocytosis in submucosal secretory glands.
Developmental expression patterns of CFTR in ferret tracheal surface airway and submucosal gland epithelia.
TLDR
The partial cloning of the ferret CFTR cDNA is described which suggests that differentiation of gland progenitor cells to CFTR-expressing submucosal gland cells occurs very early within submukosal gland development and morphogenesis.
X-ray microanalysis of airway surface liquid collected in cystic fibrosis mice.
TLDR
Using a cryoprobe specifically adapted to collect native ASL from the tracheal mouse surface, this cryotechnique appears to be a promising technique for analyzing the complete elemental composition of native AsL in CF and non-CF tissues.
Submucosal glands are the predominant site of CFTR expression in the human bronchus
TLDR
The data suggest mechanisms whereby defects in CFTR expression could lead to abnormal production of mucus in human lung, particularly in non–CF individuals.
Ion composition and rheology of airway liquid from cystic fibrosis fetal tracheal xenografts.
TLDR
The results suggest that prior to inflammation and infection, the viscosity and ion composition of the fetal AL do not differ in CF and non-CF.
...
1
2
3
4
5
...