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

Traffic-related air pollution (TRAP) exposure is associated with systemic health effects, which can be studied using blood-based markers. Although the authors 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. The authors 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 PM₂.₅ for 4h, separated by ≥ 4-week washouts. The authors 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, the authors 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 PM₂.₅, 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 PM₂.₅ (−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.

• Record URL:
  • https://doi.org/10.1016/j.envpol.2023.123087
• Record URL:
  • http://www.sciencedirect.com/science/article/pii/S0269749123020894
• Availability:
  • Find a library where document is available. Order URL: http://worldcat.org/issn/02697491
• Supplemental Notes:
  • © 2023 Published by Elsevier Ltd. Abstract reprinted with permission of Elsevier.
• Authors:
  • Orach, Juma
  • 0000-0002-9676-7921
  • Hemshekhar, Mahadevappa
  • Rider, Christopher Francis
  • Spicer, Victor
  • Lee, Amy H
  • Yuen, Agnes Che Yan
  • Mookherjee, Neeloffer
  • 0000-0002-9350-4157
  • Carlsten, Chris
• Publication Date: 2024-2-1

Language

• English

Media Info

• Media Type: Web
• Features: References;
• Pagination: 123087
• Serial:
  • Environmental Pollution
  • Volume: 342
  • Issue Number: 0
  • Publisher: Elsevier Publishing Company, Limited
  • ISSN: 0269-7491
  • Serial URL: http://www.journals.elsevier.com/environmental-pollution

Subject/Index Terms

• TRT Terms: Air pollution; Diesel engine exhaust gases; Public health; Respiratory system
• Subject Areas: Environment; Highways;

Filing Info

• Accession Number: 01913146
• Record Type: Publication
• Files: TRIS
• Created Date: Mar 27 2024 11:52AM