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

Autor: Orach J; 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., Hemshekhar M; Manitoba Center for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Manitoba, Winnipeg, R3E 3P4, Canada., Rider CF; 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., Spicer V; Manitoba Center for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Manitoba, Winnipeg, R3E 3P4, Canada., Lee AH; Molecular Biology and Biochemistry, Department of Molecular Biology and Biochemistry, Simon Fraser University, British Columbia, Burnaby, V5A 1S6, Canada., Yuen ACY; 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., Mookherjee N; 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., Carlsten C; 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.
Jazyk: angličtina
Zdroj: Environmental pollution (Barking, Essex : 1987) [Environ Pollut] 2024 Feb 01; Vol. 342, pp. 123087. Date of Electronic Publication: 2023 Dec 05.
DOI: 10.1016/j.envpol.2023.123087
Abstrakt: 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/m 3 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 (FEV 1 ) and methacholine provocation concentration causing a 20% drop in FEV 1 (PC 20 ). 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/m 3 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/m 3 PM 2.5 (-2.93 ± 1.18, p = 0.02). CFI levels were correlated with FEV 1 , PC 20 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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