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

Our plain-English summary of Copper-enriched automotive brake wear particles perturb human alveolar cellular homeostasis, by J.G.H. Parkin, L.S.N. Dean, J.A. Bell, et al (Particle and Fibre Toxicology, 2025).

The study

• Authors: J.G.H. Parkin, L.S.N. Dean, J.A. Bell, N.H.C. Easton, L.J. Edgeway, M.J. Cooper, R. Ridley, F. Conforti, S. Wang, L. Yao, J. Li, H.V. Raj, J. Downward, M. Gerlofs-Nijland, F.R. Cassee, Y. Wang, R.B. Cook, M.G. Jones, D.E. Davies, M. Loxham
• Journal: Particle and Fibre Toxicology
• Published: 2025;22(1):4
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2025. The Author(s).

In plain English

This laboratory study of vehicle particles was not about asbestos exposure; the article notes that non-asbestos organic (NAO) brake pads were developed to replace asbestos-containing pads, with copper fibres added for thermal conductivity. The authors collected brake-wear PM2.5–0.1 from four brake pad types (low-metallic, semi-metallic with limited copper, NAO, and ceramic) plus diesel exhaust PM, and exposed an immortalised human alveolar type-II (ATII) epithelial cell line, with some experiments in primary ATII cells. NAO and ceramic brake-wear PM produced the greatest reactive oxygen species generation, the only significant IL-6 and IL-8 release, and the most differentially expressed genes (2212 and 2153, versus 569 for low-metallic, 78 for semi-metallic with limited copper and 767 for diesel). Copper was 16-fold higher in NAO and ceramic PM than low-metallic, 68-fold higher than semi-metallic, and 300-fold higher than diesel PM. With the copper-selective chelator TEPA, NAO brake-wear PM no longer significantly increased two markers (HMOX1 and MT1G), and IL-6 secretion and HIF1α stabilisation were reduced. The authors concluded copper is a key determinant of brake-wear PM effects on alveolar cells.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory in vitro toxicology study of collected vehicle-derived particulate matter in human alveolar epithelial cells, with chemical analysis, RNA-Seq, metabolic assays and reporter assays
• Who was studied: An immortalised human alveolar type-II (ATII) epithelial cell line, with confirmatory experiments in primary ATII cells isolated from surplus macroscopically normal human lung tissue (Southampton, UK)
• Exposure: Brake-wear PM2.5–0.1 from four brake pad types (low-metallic, semi-metallic with limited copper, non-asbestos organic, ceramic) and diesel exhaust PM, mostly at 8 µg/cm2 for 2–24 h; cytotoxicity tested up to 32 µg/cm2
• Main results:
  • Cytotoxicity (LDH release) rose with concentration for NAO and ceramic brake-wear PM, and for diesel PM at 32 µg/cm2; no PM type caused a significant increase at 8 µg/cm2, the concentration used thereafter
  • Reactive oxygen species generation in ATII cells was greatest with NAO and ceramic brake-wear PM; low-metallic and diesel PM showed no significant effect
  • Only NAO and ceramic brake-wear PM significantly increased IL-6 and IL-8 secretion from the ATII cell line
  • Differentially expressed genes versus control: NAO 2212 and ceramic 2153, compared with LowM 569, SemiMxCu 78 and diesel exhaust PM 767
  • Copper content of the PM types measured by ICP-MS: NAO and ceramic brake-wear PM were far more copper-enriched than the other sources
  • With the copper-selective chelator TEPA, NAO brake-wear PM no longer significantly increased HMOX1 or MT1G; iron- and zinc-selective chelators did not prevent these responses
  • Among the chelators tested, co-exposure with copper-selective TEPA gave the largest reduction in IL-6 secretion caused by NAO brake-wear PM
  • NAO brake-wear PM significantly increased HIF1α stabilisation in ATII cells; this was diminished by ascorbate pre-treatment and, in the authors' word, abrogated by co-treatment with TEPA
  • NAO and ceramic brake-wear PM significantly increased the HIF gene-signature score, which correlated with the oxidative stress score (r = 0.90, p < 0.001); PM copper concentration correlated with oxidative stress score (r = 0.89, p < 0.05)
• The authors' conclusion: The authors concluded that copper is a key determinant of brake-wear PM's ability to perturb alveolar epithelial cell homeostasis, and that copper-enriched brake-wear PM had a greater detrimental effect than diesel exhaust PM, suggesting regulation should also target non-exhaust PM and specific PM components
• Limitations the authors state:
  • The study focused on metals, so other potentially toxic components of the particles, such as organic compounds, were not examined
  • Toxicity was assessed in 2D monocultures rather than more complex 3D multi-cell models of inhalation
  • The particle concentration used is likely higher than real-life in vivo exposures

Topics

The National Library of Medicine indexes this study under subjects our site covers: Auto mechanics and brake work.

Medical terms in this study, explained in our Lexicon: Brake Lining, Oxidative Stress, Inflammation, Pulmonary Fibrosis.

Related studies

• Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation — H. Barosova, S. Chortarea, et al. (2018)
• Airborne brake wear debris: size distributions, composition, and a comparison of dynamometer and vehicle tests — P.G. Sanders, N. Xu, et al. (2003)
• IL-8 response of cyclically stretching alveolar epithelial cells exposed to non-fibrous particles — S.M. Mijailovich, K. Hamada, et al. (2007)
• Evaluation of exposure to the airborne asbestos in an automobile brake and clutch manufacturing industry in Iran — H. Kakooei, H. Marioryad (2010)
• Inhalable particles and pulmonary host defense: in vivo and in vitro effects of ambient air and combustion particles — G.E. Hatch, E. Boykin, et al. (1985)
• Evaluation of asbestos exposure during brake repair and replacement — H. Kakooei, M. Hormozy, et al. (2011)

Browse more research in Particle and Fibre Toxicology, or return to medical research.