Copper-enriched automotive brake wear particles perturb human alveolar cellular homeostasis.

Yihua Wang, Miriam Gerlofs-Nijland, Helen Vethakan Raj, Robert Ridley, Liam J Edgeway, Natasha H C Easton, James G H Parkin, Joseph A Bell, Siyuan Wang, Juanjuan Li, Lareb S N Dean, Mark G Jones, Donna E Davies, Flemming R Cassee, Richard B Cook, Matthew Loxham, Matthew J Cooper, Julian Downward, Franco Conforti, Liudi Yao

Journal: Particle and fibre toxicology 2025;22(1):4

PMID: 39940013

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Abstract

BACKGROUND

Airborne fine particulate matter with diameter < 2.5 μm (PM2.5), can reach the alveolar regions of the lungs, and is associated with over 4 million premature deaths per year worldwide. However, the source-specific consequences of PM2.5 exposure remain poorly understood. A major, but unregulated source is car brake wear, which exhaust emission reduction measures have not diminished.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Address: School of Clinical and Experimental Sciences, University of Southampton, Southampton, UK. [email protected].; School of Clinical and Experimental Sciences, University of Southampton, Southampton, UK.; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK.; Southampton Marine and Maritime Institute, University of Southampton, Boldrewood Innovation Campus, Southampton, UK.; School of Clinical and Experimental Sciences, University of Southampton, Southampton, UK.; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK.; School of Clinical and Experimental Sciences, University of Southampton, Southampton, UK.; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK.; Southampton Marine and Maritime Institute, University of Southampton, Boldrewood Innovation Campus, Southampton, UK.; School of Ocean and Earth Sciences, University of Southampton, Southampton, UK.; School of Clinical and Experimental Sciences, University of Southampton, Southampton, UK.; Institute for Life Sciences, University of Southampton, Highfield Campus, Southampton, UK.; School of Ocean and Earth Sciences, University of Southampton, Southampton, UK.; School of Clinical and Experimental Sciences, University of Southampton, Southampton, UK.; Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.; Oncogene Biology Laboratory, The Francis Crick Institute, London, UK.; National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.; National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.; Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.; Institute for Life Sciences, University of Southampton, Highfield Campus, Southampton, UK.; Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.; National Centre for Advanced Tribology (nCATS), Mechanical Engineering, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, UK.; School of Clinical and Experimental Sciences, University of Southampton, Southampton, UK.; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK.; Institute for Life Sciences, University of Southampton, Highfield Campus, Southampton, UK.; School of Clinical and Experimental Sciences, University of Southampton, Southampton, UK. [email protected].; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK. [email protected].; Southampton Marine and Maritime Institute, University of Southampton, Boldrewood Innovation Campus, Southampton, UK. [email protected].; Institute for Life Sciences, University of Southampton, Highfield Campus, Southampton, UK. [email protected].

DOI: 10.1186/s12989-024-00617-2

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MeSH Terms: Humans, Copper, Particulate Matter, Vehicle Emissions, Homeostasis, Automobiles, Air Pollutants, Oxidative Stress, Particle Size, Pulmonary Alveoli