Concentration-dependent alterations in the human plasma proteome following controlled exposure to diesel exhaust

Juma Orach; Mahadevappa Hemshekhar; Christopher Francis Rider; Victor Spicer; Amy H Lee; Agnes Che Yan Yuen; Neeloffer Mookherjee; Chris Carlsten

doi:10.1016/j.envpol.2023.123087

Concentration-dependent alterations in the human plasma proteome following controlled exposure to diesel exhaust

Environ Pollut. 2024 Feb 1:342:123087. doi: 10.1016/j.envpol.2023.123087. Epub 2023 Dec 5.

Authors

Juma Orach¹, Mahadevappa Hemshekhar², Christopher Francis Rider¹, Victor Spicer², Amy H Lee³, Agnes Che Yan Yuen¹, Neeloffer Mookherjee⁴, Chris Carlsten⁵

Affiliations

¹ Air Pollution Exposure Laboratory, Division of Respiratory Medicine, Department of Medicine, Vancouver Coastal Health Research Institute, The University of British Columbia, British Columbia, Vancouver, V5Z1W9, Canada.
² Manitoba Center for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Manitoba, Winnipeg, R3E 3P4, Canada.
³ Molecular Biology and Biochemistry, Department of Molecular Biology and Biochemistry, Simon Fraser University, British Columbia, Burnaby, V5A 1S6, Canada.
⁴ Manitoba Center for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Manitoba, Winnipeg, R3E 3P4, Canada; Department of Immunology, University of Manitoba, Manitoba, Winnipeg, R3E 0T5, Canada.
⁵ Air Pollution Exposure Laboratory, Division of Respiratory Medicine, Department of Medicine, Vancouver Coastal Health Research Institute, The University of British Columbia, British Columbia, Vancouver, V5Z1W9, Canada. Electronic address: carlsten@mail.ubc.ca.

PMID: 38061431
DOI: 10.1016/j.envpol.2023.123087

Abstract

Traffic-related air pollution (TRAP) exposure is associated with systemic health effects, which can be studied using blood-based markers. Although we have previously shown that high TRAP concentrations alter the plasma proteome, the concentration-response relationship between blood proteins and TRAP is unexplored in controlled human exposure studies. We aimed to identify concentration-dependent plasma markers of diesel exhaust (DE), a model of TRAP. Fifteen healthy non-smokers were enrolled into a double-blinded, crossover study where they were exposed to filtered air (FA) and DE at 20, 50 and 150 μg/m³ PM_2.5 for 4h, separated by ≥ 4-week washouts. We collected blood at 24h post-exposure and used label-free mass spectrometry to quantify proteins in plasma. Proteins exhibiting a concentration-response, as determined by linear mixed effects models (LMEMs), were assessed for pathway enrichment using WebGestalt. Top candidates, identified by sparse partial least squares discriminant analysis and LMEMs, were confirmed using enzyme-linked immunoassays. Thereafter, we assessed correlations between proteins that showed a DE concentration-response and acute inflammatory endpoints, forced expiratory volume in 1 s (FEV₁) and methacholine provocation concentration causing a 20% drop in FEV₁ (PC₂₀). DE exposure was associated with concentration-dependent alterations in 45 proteins, which were enriched in complement pathways. Of the 9 proteins selected for confirmatory immunoassays, based on complementary bioinformatic approaches to narrow targets and availability of high-quality assays, complement factor I (CFI) exhibited a significant concentration-dependent decrease (-0.02 μg/mL per μg/m³ of PM_2.5, p = 0.04). Comparing to FA at discrete concentrations, CFI trended downward at 50 (-2.14 ± 1.18, p = 0.08) and significantly decreased at 150 μg/m³ PM_2.5 (-2.93 ± 1.18, p = 0.02). CFI levels were correlated with FEV₁, PC₂₀ and nasal interleukin (IL)-6 and IL-1β. This study details concentration-dependent alterations in the plasma proteome following DE exposure at concentrations relevant to occupational and community settings. CFI shows a robust concentration-response and association with established measures of airway function and inflammation.

Keywords: Concentration-response; Controlled human exposures; Inflammation; Proteomics; Traffic-related pollution.

MeSH terms

Air Pollutants* / analysis
Air Pollutants* / toxicity
Cross-Over Studies
Humans
Interleukin-6
Particulate Matter / analysis
Particulate Matter / toxicity
Proteome
Respiratory Function Tests
Vehicle Emissions* / analysis
Vehicle Emissions* / toxicity

Substances

Vehicle Emissions
Proteome
Interleukin-6
Particulate Matter
Air Pollutants