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Many people are exposed every day to vehicle exhaust particulates (VEPs), which are thought to be taken up by epithelial cells that are the first barrier in our biological defense. The study aim was to investigate how VEPs are processed in the lysosomal degradation system. BEAS-2B airway epithelial cells easily ingest VEPs and have been shown to accumulate in cells for several days, but no elevated cytotoxicity was observed over that time period. An analysis of 3D images confirmed the presence of VEPs in or near lysosomes, and an accumulation of VEPs resulted in an increase in the normal acidic pH in lysosomes and the extracellular release of the lysosomal enzyme β-hexosaminidase. Epithelial cells were thought to activate the lysosome-mediated secretion of extracellular vesicles to avoid damage caused by non-degradable foreign substances, such as VEPs, and as a side reaction, the acidic pH environment of the lysosomes could not be maintained.