title: Single Exposure to near Roadway Particulate Matter Leads to Confined Inflammatory and Defense Responses: Possible Role of Metals.
abstract: Inhalation of traffic-associated atmospheric particulate matter (PM2.5) is recognized as a significant health risk. In this study, we focused on a single ("subclinical response") exposure to water-soluble extracts from PM collected at a roadside site in a major European city to elucidate potential components that drive pulmonary inflammatory, oxidative, and defense mechanisms and their systemic impacts. Intratracheal instillation (IT) of the aqueous extracts induced a 24 h inflammatory response characterized by increased broncho-alveolar lavage fluid (BALF) cells and cytokines (IL-6 and TNF-α), increased reactive oxygen species production, but insignificant lipids and proteins oxidation adducts in mouse lungs. This local response was largely self-resolved by 48 h, suggesting that it could represent a subclinical response to everyday-level exposure. Removal of soluble metals by chelation markedly diminished the pulmonary PM-mediated response. An artificial metal solution (MS) recapitulated the PM extract response. The self-resolving nature of the response is associated with activating defense mechanisms (increased levels of catalase and glutathione peroxidase expression), observed with both PM extract and MS. In conclusion, metals present in PM collected near roadways are largely responsible for the observed transient local pulmonary inflammation and oxidative stress. Simultaneous activation of the antioxidant defense response may protect against oxidative damage.
authors.affiliation: †Department of Earth and Planetary Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Pardo
authors.affiliation: ‡Environmental Chemistry and Technology Program, University of Wisconsin-Madison, Madison, Wisconsin, United States.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Shafer
authors.affiliation: §Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, and the National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Rudich
authors.affiliation: ‡Environmental Chemistry and Technology Program, University of Wisconsin-Madison, Madison, Wisconsin, United States.
authors.forename: James J
authors.initials: JJ
authors.lastname: Schauer
authors.affiliation: †Department of Earth and Planetary Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yinon
authors.initials: Y
authors.lastname: Rudich
mesh_terms: D000393:Air Pollutants / Q000032:analysis; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002947:Cities; D004781:Environmental Exposure / Q000032:analysis*; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008131:London; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008670:Metals / Q000633:toxicity*; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012996:Solutions; D014186:Transportation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D000975:Antioxidants; D015850:Interleukin-6; D008670:Metals; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D012996:Solutions; D014409:Tumor Necrosis Factor-alpha