Different Susceptibility to Particulate Matter Exposure within the Respiratory Tract

Poster (konferens), 2026

Air pollution contributes to millions of premature deaths annually. Inhaled particulate matter (PM) can deposit on the airway epithelium, triggering oxidative stress and inflammation. Long-term exposure to even low levels of PM has been linked to severity in chronic lung disorders as asthma and chronic obstructive pulmonary disease (COPD). Inhalation of PM may promote acute exacerbations accelerating the rate of pulmonary decline and resulting in hypoxic conditions. Most in vitro PM studies are limited by using a single cell type, a single short exposure duration, and simplified PM samples. In addition, the combined effects of PM exposure and hypoxic conditions on the airway epithelium remain inconclusive. In our previous studies, bronchial epithelial cells responded to hypoxia with more pathological inflammation and remodeling (Berggren-Nylund et al, 2023). This response was further aggravated by profibrotic stimuli, implying that individuals with chronic or prolonged hypoxia are more susceptible to PM toxicity.
The aim of this study was to evaluate the effect of PM exposure on viability and inflammatory responses in alveolar and bronchial epithelial cells and determine whether these effects are exacerbated when combined with hypoxia. Human alveolar epithelial (H441) and bronchial epithelial (BEAS-2B) cells were exposed to 1, 10 or 100 μg/mL of different PM2.5 and PM10 samples or carbon black for 24, 48 or 72 hours. The PM samples were collected from different areas in London, UK, and in Gårda, Gothenburg, Sweden. Changes in cell viability were determined using LDH assay to quantify cytotoxicity and WST-1 assay to quantify metabolic activity and reactive oxygen species (ROS) were measured. Multiplex analyses, measuring different pro-inflammatory cytokines and growth factors, were performed after 24 h of PMexposure with or without hypoxic conditions (1% O2). Our data show that cytotoxicity increased with higher PM concentrations and exposure time in both alveolar and bronchial epithelial cells. Metabolic activity of alveolar epithelial cells decreased with increasing PM concentration and exposure time, whereas the inverse was seen in bronchial epithelial cells. IL-6 levels increased in both alveolar and bronchial epithelial cells following PM exposure and the release was further increased in alveolar cells during hypoxia. In conclusion, PM size, concentration and source influenced the toxic effects with increased cytotoxicity over time. Additionally, there were distinct differences in response to PM exposure in alveolar and bronchial epithelial cells, where alveolar cells appear more vulnerable. This highlights the need of further research to elucidate the different susceptibility to PM within the respiratory tract, to better inform air quality regulations.