Journal
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Volume 24, Issue 2, Pages 195-202Publisher
AMER THORACIC SOC
DOI: 10.1165/ajrcmb.24.2.3918
Keywords
-
Funding
- NIDDK NIH HHS [R01 DK47967, P30 DK25295, P30 DK54759, R01 DK047967] Funding Source: Medline
Ask authors/readers for more resources
Antibacterial defenses in the airway are dependent on multifactorial influences that determine the composition of both fluid and/or electrolytes at the surface of the airway and the secretory products that aid in bacterial killing and clearance. In cystic fibrosis (CF), these mechanisms of airway protection may be defective, leading to increased colonization with Pseudomonas aeruginosa. Submucosal glands, a predominant site of cystic fibrosis transmembrane conductance regulator (CFTR) protein expression in the airway, have been hypothesized to play an important role in protection of the airway, Furthermore, recent studies have suggested that the salt concentration at the airway surface may be a key factor in regulating the activity of antibacterial substances in the airway, To explore these issues, we have used a new model of the ferret tracheal airway to evaluate the contribution of submucosal glands in regulating airway surface fluid and electrolyte composition. Using tracheal xenograft models with and without submucosal glands, we have characterized several aspects of airway physiology that may be important in defining antibacterial properties, These endpoints included the contribution of submucosal glands in defining bioelectric properties of the surface airway epithelium, airway surface fluid (ASF) chloride composition, ASF volumes, and secretion of the antibacterial factor lysozyme, Findings from these studies demonstrate a significantly elevated secreted fluid volume (Vs) and chloride concentration ([CI],) in ASF from airways with submucosal glands (Vs = 47 +/- 4 mul; [CI](S) = 128 +/- 5 mM), as compared with xenograft airways without glands (Vs = 36 +/- 2 mul; [CI](S) = 103 +/- 6 mM), Furthermore, a temperature labile factor secreted by submucosal glands appears to alter the baseline activation of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and/or diphenylamine-2-carboxylic acid-sensitive chloride channels in the surface airway epithelium. Lastly, the lysozyme content of tracheal airways with submucosal glands was 8.5-fold higher than were airways without glands. These studies demonstrate that submucosal glands affect both the ionic composition and bioelectric properties of the airway and suggest that models evaluating antibacterial properties of the airway in CF should take into account the contribution of glands in airway physiology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available