title: Associations of urban air particulate composition with inflammatory and cytotoxic responses in RAW 246.7 cell line.
abstract: Epidemiological studies show heterogeneities in the particulate pollution-related exposure-effect relationships among cardiorespiratory patients, but the connection to chemical composition and toxic properties of the inhaled particles is largely unknown. To identify the chemical constituents and sources responsible for the diverse inflammatory and cytotoxic effects of urban air, fine (PM(2.5-0.2)) and coarse (PM(10-2.5)) particulate samples were collected during contrasting air pollution situations. We exposed mouse RAW 246.7 macrophages for 24 hrs to PM(2.5-0.2) and PM(10-2.5) samples from six European cities. The concentrations of proinflammatory cytokines (IL-6, TNFalpha), chemokine (MIP-2), and nitric oxide were measured from the cell culture medium, and the cytotoxicity was assayed. Spearman's correlations between the chemical constituents and cellular responses were analyzed. In the PM(2.5-0.2) size range, the tracers of photo-oxidation of organics in the atmosphere (oxalate, succinate, malonate), some transition metals (Ni, V, Fe, Cu, Cr), and insoluble soil constituents (Ca, Al, Fe, Si) correlated positively with the response parameters. In contrast, the tracers of incomplete biomass (monosaccharide anhydrides) and coal (As) combustion, and polycyclic aromatic hydrocarbons (PAHs), had negative correlations with the inflammatory activity. The compositions of PM(10-2.5) samples were more uniform and there were only occasional high correlations between the chemical constituents, endotoxin, and the response parameters. The present results suggest that the local sources of incomplete combustion and resuspended road dust are important producers of harmful fine particulate constituents that may, however, operate via diverse toxicity mechanisms. The results agree well with our recent findings in the mouse lung.
authors.affiliation: Department of Environmental Health, National Institute for Health & Welfare (THL), Kuopio, Finland. pasi.jalava@thl.fi
authors.forename: Pasi I
authors.initials: PI
authors.lastname: Jalava
authors.forename: Maija-Riitta
authors.initials: MR
authors.lastname: Hirvonen
authors.forename: Markus
authors.initials: M
authors.lastname: Sillanpää
authors.forename: Arto S
authors.initials: AS
authors.lastname: Pennanen
authors.forename: Mikko S
authors.initials: MS
authors.lastname: Happo
authors.forename: Risto
authors.initials: R
authors.lastname: Hillamo
authors.forename: Flemming R
authors.initials: FR
authors.lastname: Cassee
authors.forename: Miriam
authors.initials: M
authors.lastname: Gerlofs-Nijland
authors.forename: Paul J A
authors.initials: PJ
authors.lastname: Borm
authors.forename: Roel P F
authors.initials: RP
authors.lastname: Schins
authors.forename: Nicole A H
authors.initials: NA
authors.lastname: Janssen
authors.forename: Raimo O
authors.initials: RO
authors.lastname: Salonen
mesh_terms: D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D004396:Coloring Agents; D016207:Cytokines / Q000096:biosynthesis; D005060:Europe; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014867:Water / Q000032:analysis
chemical_list: D000393:Air Pollutants; D018925:Chemokines; D004396:Coloring Agents; D016207:Cytokines; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D009569:Nitric Oxide; C022616:thiazolyl blue