defective fluid secretion from submucosal glands of nasal turbinates from cftr-- and cftrδf508δf508 pigs有缺陷的cftr流体的鼻内窥镜鼻窦黏膜下腺体分泌物检测,cftrδf508δf508猪.pdfVIP

Defective Fluid Secretion from Submucosal Glands of Nasal Turbinates from CFTR-/- and CFTRDF508/DF508 Pigs Hyung-Ju Cho*, Nam Soo Joo, Jeffrey J. Wine Cystic Fibrosis Research Laboratory, Psychology Department, Stanford University, Stanford, California, United States of America Abstract Background: 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 mM forskolin: 9.262.2 vs. 0.660.3; 1 mM carbachol: 143.5635.5 vs. 52.2610.3; 3 mM forskolin + 0.1 mM carbachol: 25.8 65.8 vs. CF 4.560.9. We also compared CFDF508/DF508 with CFTR-/- piglets and found significantly greater forskolin-stimulated secretion rates in the DF508 vs. the null piglets (1.460.8, n = 4 vs. 0.2 60.1, n = 7). An unexpected age effect was also discovered: the ratio of secretion to 3 mM forskolin vs. 1 mM carbachol was ,4 times greater in adult than in neonatal nasal glands. Conclusions/Significance: These findings