title: Inflammation and tissue damage in mouse lung by single and repeated dosing of urban air coarse and fine particles collected from six European cities.
abstract: The authors have previously demonstrated heterogeneities in the inflammatory activities of urban air fine (PM(2.5-0.2)) and coarse (PM(10-2.5)) particulate samples collected from six European cities with contrasting air pollution situations. The same samples (10 mg/kg) were intratracheally instilled to healthy C57BL/6J mice either once or repeatedly on days 1, 3, and 6 of the study week. The lungs were lavaged 24 h after the single dose or after the last repeated dosing. In both size ranges, repeated dosing of particles increased the total cell number in bronchoalveolar lavage fluid (BALF) more than the respective single dose, whereas cytokine concentrations were lower after repeated dosing. The lactate dehydrogenase (LDH) responses increased up to 2-fold after repeated dosing of PM(2.5-0.2) samples and up to 6-fold after repeated dosing of PM(10-2.5) samples. PM(10-2.5) samples evoked a more extensive interstitial inflammation in the mouse lungs. The constituents with major contributions to the inflammatory responses were oxidized organic compounds and transition metals in PM(2.5-0.2) samples, Cu and soil minerals in PM(10-2.5) samples, and Zn in both size ranges. In contrast, poor biomass and coal combustion were associated with elevated levels of polycyclic aromatic hydrocarbons (PAHs) and a consistent inhibitory effect on the inflammatory activity of PM(2.5-0.2) samples. In conclusion, repeated intratracheal instillation of both fine and coarse particulate samples evoked enhanced pulmonary inflammation and cytotoxicity compared to single-dose administration. The sources and constituents of urban air particles responsible for these effects appear to be similar to those encountered in the authors' previous single-dose study.
authors.affiliation: National Institute for Health and Welfare, Department of Environmental Health, Kuopio, Finland. Mikko.Happo@thl.fi
authors.forename: M S
authors.initials: MS
authors.lastname: Happo
authors.forename: R O
authors.initials: RO
authors.lastname: Salonen
authors.forename: A I
authors.initials: AI
authors.lastname: Hälinen
authors.forename: P I
authors.initials: PI
authors.lastname: Jalava
authors.forename: A S
authors.initials: AS
authors.lastname: Pennanen
authors.forename: J A M A
authors.initials: JA
authors.lastname: Dormans
authors.forename: M E
authors.initials: ME
authors.lastname: Gerlofs-Nijland
authors.forename: F R
authors.initials: FR
authors.lastname: Cassee
authors.forename: V-M
authors.initials: VM
authors.lastname: Kosma
authors.forename: M
authors.initials: M
authors.lastname: Sillanpää
authors.forename: R
authors.initials: R
authors.lastname: Hillamo
authors.forename: M-R
authors.initials: MR
authors.lastname: Hirvonen
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000397:Air Pollution / Q000032:analysis; D000818:Animals; D002947:Cities; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004784:Environmental Monitoring; D005060:Europe; D007442:Intubation, Intratracheal; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052638:Particulate Matter / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D013047:Specific Pathogen-Free Organisms
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D052638:Particulate Matter; D007770:L-Lactate Dehydrogenase