119 Differential Alveolar Toxicity of Exhaust and Non-Exhaust Fine Particulate Matter

Annals of Work Exposures and Health(2023)

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Abstract Introduction Airborne fine particulate matter (diameter <2.5μm; PM2.5) is a leading risk factor for ill health and premature death. Road vehicle technology is decreasing exhaust-derived PM emissions but poorly characterised, unregulated non-exhaust PM persists. This study aimed to characterise the toxicology of brakewear PM2.5 (BWPM) from 4 brakepad types, and roadwear PM, compared to diesel exhaust PM2.5 (DEP). Methods An alveolar type-II epithelial cell line (ATIIER:KRASv12) was exposed to 3.9-31.6µg/cm2 PM2.5 generated from 4 brake pad types (low-metallic/semi-metallic/non-asbestos organic [NAO]/ceramic), roadwear, or DEP for 2-24h. PM composition was determined by ICP-MS, cytotoxicity by LDH and MTT assays, cytokine release by ELISA, gene expression by RT-qPCR and RNA-Seq, and protein expression by western blot. Results NAO and ceramic BWPM, enriched in copper and zirconium, exerted greatest increases in cytotoxicity, cytokine release (IL-6: NAO 26-fold, ceramic 20-fold; p<0.05), and oxidative stress-related (HMOX1 – NAO 28-fold, ceramic 26-fold, p<0.001) and metal homeostasis genes (MT1G: NAO 197-fold, ceramic 183-fold; p<0.001), consistently greater than roadwear PM or DEP. Amelioration by copper-chelating tetraethylenepentamine implicated BWPM copper. RNA-Seq showed NAO and ceramic BWPM induced most differentially expressed genes vs. control, related to inflammatory, oxidative stress, heat-shock, and hypoxia responses. Effects on hypoxia signalling were confirmed through HIF1α western blot and HIF-signalling reporter assay. Conclusions NAO and ceramic BWPM were the most potent across multiple endpoints. Future work will study the relevance of HIF-related responses, which have been implicated in fibrotic lung disease. Understanding source-dependent toxicity may facilitate manufacturing- and healthcare-related mitigation of PM toxicity.
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关键词
differential alveolar toxicity,particulate matter,non-exhaust
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