Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease.
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, altered inflammatory response, defective organellar acidification, loss of CFTR regulation of plasma membrane ion transporters, and others. This review focuses on the physiology of the ASL and submucosal glands with regard to their proposed role in CF lung disease. Experimental evidence for defective ASL properties and gland function in CF is reviewed, and deficiencies in understanding ASL/gland physiology are identified as areas for further investigation. New model systems and measurement technologies are being developed to make progress in establishing lung disease mechanisms in CF, which should facilitate mechanism-based design of therapies for CF.
Verkman
A S
AS
Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California-San Francisco, 1246 Health Sciences East Tower, San Francisco, CA 94143-0521, USA. verkman@itsa.ucsf.edu
Song
Yuanlin
Y
Thiagarajah
Jay R
JR
D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology; D005088:Exocrine Glands / Q000033:anatomy & histology / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000502:physiology*; D020545:Respiratory Mucosa / Q000502:physiology*; D013499:Surface Properties
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator