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.
