title: Analysis of air pollution particulate-mediated oxidant stress in alveolar macrophages.
abstract: Adverse health effects of urban air pollution particulates may be attributable to particle-mediated oxidant stress and inflammation. Intracellular oxidant production in normal hamster alveolar macrophages (AMs) was measured upon exposure to concentrated ambient particulates (CAPs), residual oil fly ash (ROFA), and their water-soluble and particulate fractions. ROFA and CAPs caused increases in dichlorofluorescin (DCFH) oxidation, a fluorescent measure of intracellular reactive oxygen species (ROS) production, comparable to the positive control, phorbol myristate acetate (PMA). The water-soluble component of both CAPs and ROFA (CAPs, S and ROFA, S) significantly increased AM oxidant production over negative control. CAPs samples and components showed substantial day-to-day variability in their oxidant effects. Metal chelation by desferrioxamine (DF, 1 mM) caused significant inhibition of particulate-induced AM oxidant production. ROFA exposure resulted in increased macrophage inflammatory protein-2 (MIP-2) message in AMs and in increased tumor necrosis factor alpha (TNF-alpha) production by the monocyte-macrophage cell line, RAW 264.7. TNF-alpha production was inhibitable by the antioxidant N-acetylcysteine (NAC). The data suggest that metal components adsorbed to urban air pollution particulates can significantly contribute to particulate ability to cause oxidant stress and cytokine production in AMs.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Goldsmith
authors.forename: A
authors.initials: A
authors.lastname: Imrich
authors.forename: H
authors.initials: H
authors.lastname: Danaee
authors.forename: Y Y
authors.initials: YY
authors.lastname: Ning
authors.forename: L
authors.initials: L
authors.lastname: Kobzik
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D002460:Cell Line; D002614:Chelating Agents; D019742:Chemokines, CC; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D003676:Deferoxamine; D004781:Environmental Exposure / Q000009:adverse effects*; D005452:Fluoresceins; D016166:Free Radical Scavengers / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D012313:RNA / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D000393:Air Pollutants; C095218:Ccl9 protein, mouse; D002614:Chelating Agents; D019742:Chemokines, CC; D016207:Cytokines; D005452:Fluoresceins; D016166:Free Radical Scavengers; D019402:Macrophage Inflammatory Proteins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C029569:diacetyldichlorofluorescein; D012313:RNA; D003676:Deferoxamine; D000111:Acetylcysteine