  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 BWNPs 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.
