Integrity of the respiratory epithelium: damage profile under the impact of the environmental pollutant NO2 under normoxic and hypoxic conditions

Introduction:

Nasal epithelium represents an effective barrier against inhalative substances. For chronic rhinosinusitis (crs) previous studies demonstrated the existence of hypoxic mucosal areas endonasally. A significant damage of the epithelium caused by the ubiquitously present environmental pollutant NO2 was verified by our group. Objective of this study was to investigate the impact of hypoxia on genotoxicity and the extent of cell damage of nasal epithelium pre-damaged by NO2.

Methods:

Nasal mucosa was obtained from 12 patients with crs. Therefrom isolated primary mucosa cells were cultivated under air-liquid interface conditions. The NO2 exposition was carried out with the subtoxic concentration of 0.1ppm for 1 hour. Subsequently cultivation took place either under normoxic or hypoxic conditions (under 1% O2). The transepithelial resistance as well as the paracellular permeabilty were determined. For the analysis of genotoxicity the comet assay was used.

Results:

Under hypoxic conditions there was a significantly stronger reduction of the transepithelial resistance as well as a higher FD4 passage. Furthermore, the measures showed an increased genotoxicity after exposition to NO2 followed by hypoxic cultivation.

Discussion:

We could demonstrate a significantly higher damage of the epithelial integrity caused by NO2 with a subsequent hypoxia in vitro. NO2 leads already in non-genotoxic and non-cytotoxic concentration under hypoxia to a damage of the epithelial barrier. Following a damage of the epithelium by NO2 there is an increased genotoxicity under hypoxia. Epithelial repair mechanisms appear to get reduced. A higher vulnerability by NO2 among patients with crs has to be postulated.

Publication History

Publication Date:
23 April 2019 (online)