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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Particle and fibre toxicology
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39940013/ |
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Table of Contents:
- Copper-enriched automotive brake wear particles perturb human alveolar cellular homeostasis. Parkin, James G H Dean, Lareb S N Bell, Joseph A Easton, Natasha H C Edgeway, Liam J Cooper, Matthew J Ridley, Robert Conforti, Franco Wang, Siyuan Yao, Liudi Li, Juanjuan Raj, Helen Vethakan Downward, Julian Gerlofs-Nijland, Miriam Cassee, Flemming R Wang, Yihua Cook, Richard B Jones, Mark G Davies, Donna E Loxham, Matthew Humans Copper Particulate Matter Vehicle Emissions Homeostasis Automobiles Air Pollutants Oxidative Stress Particle Size Pulmonary Alveoli Airborne fine particulate matter with diameter We used an interdisciplinary approach to investigate the consequences of brake-wear PM2.5 exposure upon lung alveolar cellular homeostasis using diesel exhaust PM as a comparator. This involved RNA-Seq to analyse global transcriptomic changes, metabolic analyses to investigate glycolytic reprogramming, mass spectrometry to determine PM composition, and reporter assays to provide mechanistic insight into differential effects. We identified brake-wear PM from copper-enriched non-asbestos organic, and ceramic brake pads as inducing the greatest oxidative stress, inflammation, and pseudohypoxic HIF activation (a pathway implicated in diseases associated with air pollution exposure, including cancer, and pulmonary fibrosis), as well as perturbation of metabolism, and metal homeostasis compared with brake wear PM from low- or semi-metallic pads, and also, importantly, diesel exhaust PM. Compositional and metal chelator analyses identified that differential effects were driven by copper. We demonstrate here that brake-wear PM may perturb cellular homeostasis more than diesel exhaust PM. Our findings demonstrate the potential differences in effects, not only for non-exhaust vs exhaust PM, but also amongst different sources of non-exhaust PM. This has implications for our understanding of the potential health effects of road vehicle-associated PM. More broadly, our findings illustrate the importance of PM composition on potential health effects, highlighting the need for targeted legislation to protect public health.