Long term exposure to particulate air pollution is known to increase respiratory morbidity and mortality. In urban areas with dense traffic most of these particles are generated by vehicles, via engine exhaust or wear processes. Non-exhaust particles come from wear processes such as those concerning brakes and their toxicity is little studied. To improve our understanding of the lung toxicity mechanisms of the nanometric fraction of brake wear nanoparticles (BWNPs), we studied whether these particles affect the barrier properties of the respiratory epithelium considering particle translocation, mucus production and repair efficiency. The Calu-3 cell line grown in two-compartment chambers was used to mimic the bronchial epithelial barrier. BWNPs detected by single-particle ICP-MS were shown to cross the epithelial tissue in small amounts without affecting the barrier integrity properties, because the permeability to Lucifer yellow was not increased and there was no cytotoxicity as assessed by the release of lactate-dehydrogenase. The interaction of BWNPs with the barrier did not induce a pro-inflammatory response, but increased the expression and production of MU5AC, a mucin, by a mechanism involving the epidermal growth factor receptor pathway. During a wound healing assay, BWNP-loaded cells exhibited the same ability to migrate, but those at the edge of the wound showed higher 5-ethynyl-2'-deoxyuridine incorporation, suggesting a higher proliferation rate. Altogether these results showed that BW. NPs do not exert overt cytotoxicity and inflammation but can translocate through the epithelial barrier in small amounts and increase mucus production, a key feature of acute inflammatory and chronic obstructive pulmonary diseases. Their loading in epithelial cells may impair the repair process through increased proliferation.
Keywords: Air pollution; Calu-3; Migration assay; Mucus; Single-particle ICP-MS; Translocation.
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