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Otolaryngology - Physiology - Respiratory Medicine

Defective Fluid Secretion from Submucosal Glands of Nasal Turbinates from CFTR-/- and CFTR?F508/?F508 Pigs
Published: Wednesday, August 31, 2011
Author: Hyung-Ju Cho et al.

by Hyung-Ju Cho, Nam Soo Joo, Jeffrey J. Wine


Cystic fibrosis (CF), caused by reduced CFTR function, includes severe sinonasal disease which may predispose to lung disease. Newly developed CF pigs provide models to study the onset of CF pathophysiology. We asked if glands from pig nasal turbinates have secretory responses similar to those of tracheal glands and if CF nasal glands show reduced fluid secretion.

Methodology/Principal Findings

Unexpectedly, we found that nasal glands differed from tracheal glands in five ways, being smaller, more numerous (density per airway surface area), more sensitive to carbachol, more sensitive to forskolin, and nonresponsive to Substance P (a potent agonist for pig tracheal glands). Nasal gland fluid secretion from newborn piglets (12 CF and 12 controls) in response to agonists was measured using digital imaging of mucus bubbles formed under oil. Secretion rates were significantly reduced in all conditions tested. Fluid secretory rates (Controls vs. CF, in pl/min/gland) were as follows: 3 µM forskolin: 9.2±2.2 vs. 0.6±0.3; 1 µM carbachol: 143.5±35.5 vs. 52.2±10.3; 3 µM forskolin + 0.1 µM carbachol: 25.8±5.8 vs. CF 4.5±0.9. We also compared CF?F508/?F508 with CFTR-/- piglets and found significantly greater forskolin-stimulated secretion rates in the ?F508 vs. the null piglets (1.4±0.8, n?=?4 vs. 0.2±0.1, n?=?7). An unexpected age effect was also discovered: the ratio of secretion to 3 µM forskolin vs. 1 µM carbachol was ~4 times greater in adult than in neonatal nasal glands.


These findings reveal differences between nasal and tracheal glands, show defective fluid secretion in nasal glands of CF pigs, reveal some spared function in the ?F508 vs. null piglets, and show unexpected age-dependent differences. Reduced nasal gland fluid secretion may predispose to sinonasal and lung infections.