Integrity of the respiratory epithelium: damage profile caused by the pollutant NO2

Introduction:

Nasal epithelium represents an effective barrier against inhalative substances. Patients with chronic rhinosinusitis (crs) show a damaged epithelial function. Exhaust fumes contain NO2 as a well- known toxic agent for the upper airways. Aim of the study was to investigate the mechanisms of NO2-induced cell damage in nasal epithelium.

Methods:

Nasal mucosa was obtained from 12 patients with crs. Therefrom isolated primary mucosa cells were cultivated under air-liquid interface conditions. Toxicity and DNA damage were investigated using the trypan blue test and the comet assay. The consecutive NO2-exposure was carried out with the subtoxic concentration of 0.1 ppm for 1 hour. Afterwards, the paracellular permeability and the transepithelial resistance were determined by measuring the FD4-passage. The PCR was used to analyze molecular markers of cell-cell-contacts as zonula occludens and occludin.

Results:

DNA damage was shown after NO2 exposure of 3 hours with a concentration of 0.1 ppm. The following experiments were performed with sub-genotoxic concentrations. Here, a significant reduction of the transepithelial resistance could be measured. Furthermore, an increased FD4-Passage was assessed. This illustrates a negative correlation to the transepithelial resistance. In addition, a downregulation of gene expression of the tight junction proteins zonula occludens and occludin was determined.

Discussion:

In this study a significant damage of the integrity of the nasal epithelium could be detected in vitro. Already at non-genotoxic and non-cytotoxic concentrations NO2 interferes with the epithelial barrier, which could imply a higher vulnerability for other toxic substances. Furthermore, a higher transepithelial passage for allergens could be expected, e.g.

Publication History

Publication Date:
18 April 2018 (online)