Brake dust exposure exacerbates inflammation and transiently compromises phagocytosis in macrophages

Liza Selley*, Linda Schuster, Helene Marbach, Theresa Forsthuber, Ben Forbes, Timothy W. Gant, Thomas Sandström, Nuria Camiña, Toby J. Athersuch, Ian Mudway, Abhinav Kumar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)
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Abstract

Studies have emphasised the importance of combustion-derived particles in eliciting adverse health effects, especially those produced by diesel vehicles. In contrast, few investigations have explored the potential toxicity of particles derived from tyre and brake wear, despite their significant contributions to total roadside particulate mass. The objective of this study was to compare the relative toxicity of compositionally distinct brake abrasion dust (BAD) and diesel exhaust particles (DEP) in a cellular model that is relevant to human airways. Although BAD contained considerably more metals/metalloids than DEP (as determined by inductively coupled plasma mass spectrometry) similar toxicological profiles were observed in U937 monocyte-derived macrophages following 24 h exposures to 4-25 μg ml-1 doses of either particle type. Responses to the particles were characterised by dose-dependent decreases in mitochondrial depolarisation (p ≤ 0.001), increased secretion of IL-8, IL-10 and TNF-α (p ≤ 0.05 to p ≤ 0.001) and decreased phagocytosis of S. aureus (p ≤ 0.001). This phagocytic deficit recovered, and the inflammatory response resolved when challenged cells were incubated for a further 24 h in particle-free media. These responses were abrogated by metal chelation using desferroxamine. At minimally cytotoxic doses both DEP and BAD perturbed bacterial clearance and promoted inflammatory responses in U937 cells with similar potency. These data emphasise the requirement to consider contributions of abrasion particles to traffic-related clinical health effects.

Original languageEnglish
Pages (from-to)371-386
Number of pages16
JournalMetallomics
Volume12
Issue number3
Early online date9 Jan 2020
DOIs
Publication statusPublished - Mar 2020

Bibliographical note

Funding Information: Liza Selley was supported by the Integrative Toxicology Training Partnership (ITTP) from the Medical Research Council, UK (Grant awarded to TG and TA) and a Mini Fellowship grant awarded by the In Vitro Toxicology Society, UK. TG was supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Health Impact of Environmental Hazards held at King’s College London in partnership with Public Health England (PHE) and Imperial College London. Our metal analysis was performed by the London Metallomics Facility and funded by the Wellcome trust (grant reference 202902/Z/16/Z, awarded to IM).

The authors would like to thank SMP Svensk Maskinprovning, Sweden for providing the brake abrasion dust employed in this study. The authors would also like to acknowledge Stevenage Bioscience Catalyst, GlaxoSmithKline and GE Healthcare for providing access to the IN Cell Analyzer 6000 and for training on the instrument. LSE acknowledges the MRC Integrative Toxicology Training Partnership (ITTP) and the In Vitro Toxicology Society for financial support.

Open Access: This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by/3.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Publisher Copyright: © 2020 The Royal Society of Chemistry.

Citation: Liza Selley, Linda Schuster, Helene Marbach, Theresa Forsthuber, Ben Forbes, Timothy W Gant, Thomas Sandström, Nuria Camiña, Toby J Athersuch, Ian Mudway, Abhinav Kumar, Brake dust exposure exacerbates inflammation and transiently compromises phagocytosis in macrophages, Metallomics, Volume 12, Issue 3, March 2020, Pages 371–386,

DOI:https://doi.org/10.1039/c9mt00253g

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