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Pulmonary exposure to renewable diesel exhaust particles alters protein expression and toxicity profiles in bronchoalveolar lavage fluid and plasma of mice

McCarrick, Sarah ; Malmborg, Vilhelm LU orcid ; Gren, Louise LU ; Danielsen, Pernille Høgh ; Tunér, Martin LU ; Palmberg, Lena ; Broberg, Karin ; Pagels, Joakim LU ; Vogel, Ulla and Gliga, Anda R. (2025) In Archives of Toxicology 99(2). p.797-814
Abstract

Exposure to diesel exhaust is associated with increased risk of cardiovascular and lung disease. Substituting petroleum diesel with renewable diesel can alter emission properties but the potential health effects remain unclear. This study aimed to explore toxicity and underlying mechanisms of diesel exhaust from renewable fuels. Using proximity extension assay (Olink), 92 proteins linked to inflammation, cardiovascular function, and cancer were analyzed in bronchoalveolar lavage fluid (BALF) and plasma in mice 1 day after pulmonary exposure to exhaust particles at doses of 6, 18, and 54 µg/mouse. Particles were generated from combustion of renewable (rapeseed methyl ester, RME13, hydrogen-treated vegetable oil, HVO13; both at 13%... (More)

Exposure to diesel exhaust is associated with increased risk of cardiovascular and lung disease. Substituting petroleum diesel with renewable diesel can alter emission properties but the potential health effects remain unclear. This study aimed to explore toxicity and underlying mechanisms of diesel exhaust from renewable fuels. Using proximity extension assay (Olink), 92 proteins linked to inflammation, cardiovascular function, and cancer were analyzed in bronchoalveolar lavage fluid (BALF) and plasma in mice 1 day after pulmonary exposure to exhaust particles at doses of 6, 18, and 54 µg/mouse. Particles were generated from combustion of renewable (rapeseed methyl ester, RME13, hydrogen-treated vegetable oil, HVO13; both at 13% O2 engine intake) and petroleum diesel (MK1 ultra-low-sulfur diesel at 13% and 17% O2 intake; DEP13 and DEP17). We identified positive dose–response relationships between exposure and proteins in BALF using linear models: 33 proteins for HVO13, 24 for DEP17, 22 for DEP13, and 12 for RME13 (p value < 0.05). In BALF, 11 proteins indicating cytokine signaling and inflammation (CCL2, CXCL1, CCL3L3, CSF2, IL1A, CCL20, TPP1, GDNF, LGMN, ITGB6, PDGFB) were common for all exposures. Several proteins in BALF (e.g., CCL2, CXCL1, CCL3L3, CSF2, IL1A) correlated (rs ≥ 0.5) with neutrophil cell count and DNA damage in BAL cells. Interestingly, plasma protein profiles were only affected by RME13 and, to lesser extent, by DEP13. Overall, we identified inflammation-related changes in the BALF as a common toxic mechanism for the combustion particles. Our protein-based approach enables sensitive detection of inflammatory protein changes across different matrices enhancing understanding of exhaust particle toxicity.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cytokines, Diesel exhaust particles, Intratracheal instillation, Lung inflammation, Protein profile, Renewable fuels, Systemic effects
in
Archives of Toxicology
volume
99
issue
2
pages
18 pages
publisher
Springer Science and Business Media B.V.
external identifiers
  • pmid:39739031
  • scopus:85213722470
ISSN
0340-5761
DOI
10.1007/s00204-024-03915-y
language
English
LU publication?
yes
id
797324be-cf60-4abb-887f-e85e59e00f00
date added to LUP
2025-03-12 15:17:24
date last changed
2025-07-03 01:36:52
@article{797324be-cf60-4abb-887f-e85e59e00f00,
  abstract     = {{<p>Exposure to diesel exhaust is associated with increased risk of cardiovascular and lung disease. Substituting petroleum diesel with renewable diesel can alter emission properties but the potential health effects remain unclear. This study aimed to explore toxicity and underlying mechanisms of diesel exhaust from renewable fuels. Using proximity extension assay (Olink), 92 proteins linked to inflammation, cardiovascular function, and cancer were analyzed in bronchoalveolar lavage fluid (BALF) and plasma in mice 1 day after pulmonary exposure to exhaust particles at doses of 6, 18, and 54 µg/mouse. Particles were generated from combustion of renewable (rapeseed methyl ester, RME13, hydrogen-treated vegetable oil, HVO13; both at 13% O<sub>2</sub> engine intake) and petroleum diesel (MK1 ultra-low-sulfur diesel at 13% and 17% O<sub>2</sub> intake; DEP13 and DEP17). We identified positive dose–response relationships between exposure and proteins in BALF using linear models: 33 proteins for HVO13, 24 for DEP17, 22 for DEP13, and 12 for RME13 (p value &lt; 0.05). In BALF, 11 proteins indicating cytokine signaling and inflammation (CCL2, CXCL1, CCL3L3, CSF2, IL1A, CCL20, TPP1, GDNF, LGMN, ITGB6, PDGFB) were common for all exposures. Several proteins in BALF (e.g., CCL2, CXCL1, CCL3L3, CSF2, IL1A) correlated (r<sub>s</sub> ≥ 0.5) with neutrophil cell count and DNA damage in BAL cells. Interestingly, plasma protein profiles were only affected by RME13 and, to lesser extent, by DEP13. Overall, we identified inflammation-related changes in the BALF as a common toxic mechanism for the combustion particles. Our protein-based approach enables sensitive detection of inflammatory protein changes across different matrices enhancing understanding of exhaust particle toxicity.</p>}},
  author       = {{McCarrick, Sarah and Malmborg, Vilhelm and Gren, Louise and Danielsen, Pernille Høgh and Tunér, Martin and Palmberg, Lena and Broberg, Karin and Pagels, Joakim and Vogel, Ulla and Gliga, Anda R.}},
  issn         = {{0340-5761}},
  keywords     = {{Cytokines; Diesel exhaust particles; Intratracheal instillation; Lung inflammation; Protein profile; Renewable fuels; Systemic effects}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{797--814}},
  publisher    = {{Springer Science and Business Media B.V.}},
  series       = {{Archives of Toxicology}},
  title        = {{Pulmonary exposure to renewable diesel exhaust particles alters protein expression and toxicity profiles in bronchoalveolar lavage fluid and plasma of mice}},
  url          = {{http://dx.doi.org/10.1007/s00204-024-03915-y}},
  doi          = {{10.1007/s00204-024-03915-y}},
  volume       = {{99}},
  year         = {{2025}},
}