Journal
AMERICAN JOURNAL OF RHINOLOGY & ALLERGY
Volume 34, Issue 6, Pages 830-837Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1945892420930975
Keywords
chronic rhinosinusitis; CFTR; cystic fibrosis; potential difference; transepithelial ion transport; sinusitis; chloride secretion; chloride channels; nasal mucosa; ussing chamber analysis
Categories
Funding
- National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute [1 R01 HL133006-04]
- National Institute of Diabetes and Digestive and Kidney Diseases [5P30DK072482-02]
- Cystic Fibrosis Foundation [ILLEK16G0]
- NIH/National Institutes of Allergy and Infectious disease [K08AI146220]
- John W. Kirklin Research and Education Foundation Fellowship Award
- UAB Faculty Development Research Award
- Cystic Fibrosis Foundation K08 Boost Award [CHO20A0-KB]
- Cystic Fibrosis Foundation Research Development Pilot grant [ROWE15R0]
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Background Epithelial ion transport regulates hydration of airway mucosal surfaces, and thus promotes effective mucociliary clearance (MCC). Decreased transepithelial Cl(-)transport may contribute to epithelial dysfunction by abrogating MCC and increasing mucus viscosity in chronic rhinosinusitis (CRS). The objective of the current study is to evaluate Cl(-)channel transport properties from cultures of human sinonasal epithelia. Methods Human sinonasal epithelia (HSNE) from patients undergoing sinus surgery were cultured at an air-liquid interface to confluence and full differentiation. The epithelial monolayers were mounted in Ussing Chambers to investigate pharmacological manipulation of ion transport. Epithelial Na(+)channel (via Amiloride), CFTR (via forskolin), and Ca2+-activated Cl(-)channel (CaCC, via UTP) transport were investigated among three different patient groups: Control, CRS and CRS with polyposis. CFTR mRNA levels were evaluated with quantitative RT-PCR. Results HSNE cultures from 18 patients (Control = 9, CRS = 6, CRS with polyposis = 3) were evaluated in 142 experiments. Summary data from the 18 patients demonstrated that stimulated CFTR-mediated anion transport (Delta I-SC) was significantly lower with CRS (7.58+/-2.24 mu A/cm(2)) compared to control (25.86+/-3.44 mu A/cm(2)) and CRS with polyposis (20.16+/-4.0 mu A/cm(2)) (p = 0.004). No statistically significant difference was found for CaCC anion transport between groups (p = 0.39). Significantly decreased mRNA (relative expression) was noted in CRS cultures (CRS = 40.83+/-1.76 vs. control = 116.2+/-24.27, p = 0.03). Conclusions A substantial decrease in the Cl(-)secretory capacity of HSNE monolayers was demonstrated in CRS subjects. Data suggest that CFTR may contribute more to abnormal ion transport in CRS than CaCC.
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