TY - JOUR
T1 - Particulate metal exposures induce plasma metabolome changes in a commuter panel study
AU - Ladva, Chandresh Nanji
AU - Golan, Rachel
AU - Liang, Donghai
AU - Greenwald, Roby
AU - Walker, Douglas I.
AU - Uppal, Karan
AU - Raysoni, Amit U.
AU - Tran, Vi Linh
AU - Yu, Tianwei
AU - Dana Flanders, W.
AU - Miller, Gary W.
AU - Jones, Dean P.
AU - Sarnat, Jeremy A.
N1 - Funding Information:
The presented research was supported by a Clean Air Research Center grant to Emory University and the Georgia Institute of Technology from the US Environmental Protection Agency (USEPA, RD834799) and the Human Exposome Research Center (HERCULES) (NIH, P30 ES019776). Shared instrumentation for metabolomics analysis was supported through the National Institutes of Health (NIH, OD018006). CL acknowledges pre-doctoral support from a training grant (NIH, T32 ES012870-13) and the Burroughs Wellcome Fund through the Molecules the Mankind Doctoral Pathway at Emory University. RG gratefully acknowledges support by a postdoctoral fellowship from the Environment and Health Fund, Jerusalem, Israel. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the USEPA. Further, USEPA does not endorse the purchase of any commercial products or services mentioned in the publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
ResearchCenter(HERCULES)(NIH,P30 ES019776).Sharedinstrumentationfor metabolomicsanalysiswassupportedthroughthe NationalInstitutesofHealth(NIH,OD018006).CL acknowledgespre-doctoralsupportfromatraining grant(NIH,T32ES012870-13)andtheBurroughs WellcomeFundthroughtheMoleculesthe MankindDoctoralPathwayatEmoryUniversity. RGgratefullyacknowledgessupportbyapost-doctoralfellowshipfromtheEnvironmentand HealthFund,Jerusalem,Israel.Thecontentofthis publicationissolelytheresponsibilityofthe authorsanddoesnotnecessarilyrepresentthe officialviewsoftheNationalInstitutesofHealthor theUSEPA.Further,USEPAdoesnotendorsethe purchaseofanycommercialproductsorservices mentionedinthepublication.Thefundershadno roleinstudydesign,datacollectionandanalysis, decisiontopublish,orpreparationofthe manuscript.
Publisher Copyright:
© 2018 Ladva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Introduction Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures. Methods A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog. Results HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response. Conclusions Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation.
AB - Introduction Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures. Methods A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog. Results HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response. Conclusions Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation.
UR - http://www.scopus.com/inward/record.url?scp=85053613928&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0203468
DO - 10.1371/journal.pone.0203468
M3 - Article
AN - SCOPUS:85053613928
SN - 1932-6203
VL - 13
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e0203468
ER -