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

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

doi:10.1186/s12989-024-00617-2

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	4
Number of pages	20
Journal	Particle and Fibre Toxicology
Volume	22
Issue number	1
DOIs	https://doi.org/10.1186/s12989-024-00617-2
Publication status	Published - 13 Feb 2025

Bibliographical note

Keywords

Air Pollutants/toxicity
Automobiles
Copper/toxicity
Homeostasis/drug effects
Humans
Oxidative Stress/drug effects
Particle Size
Particulate Matter/toxicity
Pulmonary Alveoli/drug effects
Vehicle Emissions/toxicity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/s12989-024-00617-2Licence: CC BY

s12989-024-00617-2Final published version, 3.53 MBLicence: CC BY

Cite this

Parkin, J. G. H., Dean, L. S. N., Bell, J. A., Easton, N. H. C., Edgeway, L. J., Cooper, M. J., Ridley, R., Conforti, F., Wang, S., Yao, L., Li, J., Raj, H. V., Downward, J., Gerlofs-Nijland, M., Cassee, F. R., Wang, Y., Cook, R. B., Jones, M. G., Davies, D. E., & Loxham, M. (2025). Copper-enriched automotive brake wear particles perturb human alveolar cellular homeostasis. Particle and Fibre Toxicology, 22(1), Article 4. https://doi.org/10.1186/s12989-024-00617-2

@article{d2a80a2277dd42e9b8a2dc80d67afab2,

title = "Copper-enriched automotive brake wear particles perturb human alveolar cellular homeostasis",

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.",

keywords = "Air Pollutants/toxicity, Automobiles, Copper/toxicity, Homeostasis/drug effects, Humans, Oxidative Stress/drug effects, Particle Size, Particulate Matter/toxicity, Pulmonary Alveoli/drug effects, Vehicle Emissions/toxicity",

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

note = "{\textcopyright} 2025. The Author(s).",

year = "2025",

month = feb,

day = "13",

doi = "10.1186/s12989-024-00617-2",

language = "English",

volume = "22",

journal = "Particle and Fibre Toxicology",

issn = "1743-8977",

publisher = "BioMed Central",

number = "1",

}

Parkin, JGH, Dean, LSN, Bell, JA, Easton, NHC, Edgeway, LJ, Cooper, MJ, Ridley, R, Conforti, F, Wang, S, Yao, L, Li, J, Raj, HV, Downward, J, Gerlofs-Nijland, M, Cassee, FR, Wang, Y, Cook, RB, Jones, MG, Davies, DE & Loxham, M 2025, 'Copper-enriched automotive brake wear particles perturb human alveolar cellular homeostasis', Particle and Fibre Toxicology, vol. 22, no. 1, 4. https://doi.org/10.1186/s12989-024-00617-2

TY - JOUR

T1 - Copper-enriched automotive brake wear particles perturb human alveolar cellular homeostasis

AU - Parkin, James G H

AU - Dean, Lareb S N

AU - Bell, Joseph A

AU - Easton, Natasha H C

AU - Edgeway, Liam J

AU - Cooper, Matthew J

AU - Ridley, Robert

AU - Conforti, Franco

AU - Wang, Siyuan

AU - Yao, Liudi

AU - Li, Juanjuan

AU - Raj, Helen Vethakan

AU - Downward, Julian

AU - Gerlofs-Nijland, Miriam

AU - Cassee, Flemming R

AU - Wang, Yihua

AU - Cook, Richard B

AU - Jones, Mark G

AU - Davies, Donna E

AU - Loxham, Matthew

PY - 2025/2/13

Y1 - 2025/2/13

N2 - 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.

AB - 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.

KW - Air Pollutants/toxicity

KW - Automobiles

KW - Copper/toxicity

KW - Homeostasis/drug effects

KW - Humans

KW - Oxidative Stress/drug effects

KW - Particle Size

KW - Particulate Matter/toxicity

KW - Pulmonary Alveoli/drug effects

KW - Vehicle Emissions/toxicity

U2 - 10.1186/s12989-024-00617-2

DO - 10.1186/s12989-024-00617-2

M3 - Article

C2 - 39940013

SN - 1743-8977

VL - 22

JO - Particle and Fibre Toxicology

JF - Particle and Fibre Toxicology

IS - 1

M1 - 4

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this