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.

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 PM2.5 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 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.

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