Potential toxicity of micro- and nanoplastics in primary bronchial epithelial cells of patients with chronic obstructive pulmonary disease

Abstract

Background The environmental presence of airborne micro- and nanoplastics (MNPs) raises concerns about their impact on the development and progression of respiratory diseases, including chronic obstructive pulmonary disease (COPD). In this study, we investigated the potential toxicity of amorphous, environmentally relevant MNPs in primary bronchial epithelial cells (PBEC) exposed at the air-liquid interface (ALI). Methods Differentiated PBEC cultures from COPD donors (n = 3) and non-COPD donors (n = 3) were exposed for 24 h to polyvinylchloride (PVC), polypropylene (PP), or polyamide-6,6 (PA) MNPs (> 75% of particles < 1 mu m) via small droplet application. Cytotoxicity, inflammation, cellular composition, morphology and integrity of the epithelial barrier as well as antioxidant and autophagy-related processes were assessed by a combination of lactate dehydrogenase leakage, IL-8 secretion, transmission electron microscopy and gene expression analyses. Results All PBEC cultures formed an intact epithelial barrier. However, transepithelial electrical resistance (TEER) and transcript levels of tight junction protein Claudin 4 were lower (FC = 0.36, p = 0.02) in COPD-PBEC versus non-COPD PBEC. Although with some inter-donor variability, MNPs did not induce profound cytotoxicity or inflammation. However, PA MNPs (3 <mu>g/cm(2)), decreased expression of Zonula Occludens-1 (FC = 0.76, p = 0.01), Occludin (FC = 0.75, p = 0.03) and modulated cell-type specific genes in COPD-PBEC, suggesting (early) epithelial barrier disruption. Additionally, differential regulation of transcript levels of antioxidant, apoptotic and autophagy genes was observed between COPD and non-COPD in response to PVC and PA. Conclusion These results indicate that MNP exposure, especially PA, can induce (sub)toxic effects in PBEC, with substantial inter-donor variability. Whether this impacts COPD development remains to be studied.