Cystic fibrosis (CF) is a clinical entity defined by aberrant chloride (Cl) ion transport causing downstream effects on mucociliary clearance (MCC) in sinonasal epithelia. Inducible deficiencies in transepithelial Cl transport via CF transmembrane conductance regulator (CFTR) has been theorized to be a driving process in recalcitrant chronic rhinosinusitis (CRS) in patients without CF. We have previously identified that brief exposures to bacterial lipopolysaccharide (LPS) in mammalian cells induces an acquired dysfunction of CFTR in vitro and in vivo. The objective of the current study is to evaluate whether LPS generates a model of acquired CFTR dysfunction murine nasal airways.
Basic science.
Laboratory.
CFTR murine nasal airways were irrigated with 2 µg/mL LPS or control vehicle twice daily for 1 week and transepithelial Cl transport assessed with the nasal potential difference (NPD) assay. Histopathologic evaluation included the number of lymphoid aggregates, as well as the epithelial and subepithelial heights.
Transepithelial Cl secretion by NPD was markedly reduced in mice exposed to LPS (in mV, -0.14 ± 7.7 vs control, -6.98 ± 7.15, P < .05), while amiloride-sensitive voltage was preserved (6.38 ± 5.09 vs control, 7.36 ± 2.87, P = .99). Histopathology demonstrated significantly higher lymphoid aggregates per high-power field (2.3 ± 0.9 vs 1.1 ± 0.7, control, P < .01) and increased epithelial height (in µm, 40.88 ± 13.9 vs control, 25.32 ± 6.26, P < .05).
Twice daily irrigation with LPS in murine nasal airways over 1 week led to acquired defects in transepithelial Cl transport. This animal model provides an excellent means to test the contributions of acquired CFTR dysfunction to CRS and test CFTR correctors and potentiators that might improve MCC.
© 2025 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.
