title: Pulmonary inflammation by ambient air particles is mediated by superoxide anion.
abstract: Lung inflammation is a key response to increased levels of particulate air pollution (PM); however, the cellular mechanisms leading to this response remain poorly understood. We have previously shown that oxidants are critical mediators of the inflammatory response elicited by inhalation of ambient air particles. Here we tested the possible role of a specific oxidant, superoxide anion, by using the membrane-permeable analog of superoxide dismutase, Mn(III) tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP). Adult Sprague-Dawley rats were instilled with either urban air particles (UAP) or saline. MnTBAP-treated rats received 10 mg/kg (ip) MnTBAP 2 h prior to exposure to UAP. Recruitment of inflammatory cells into bronchoalveolar lavage was evaluated 4 h after instillation. Rats exposed to UAP showed significant increases in the total cell number (8.9 +/- 0.6 x 10(6); sham: 5.1 +/- 0.6 x 10(6), p < .02), the numbers of polymorphonuclear leukocytes (26 +/- 4%; sham: 6 +/- 1%, p < .0001), protein levels (1.2 +/- 0.5 mg/ml, sham: 0.4 +/- 0.1 mg/ml, p < .001), and a trend of increase in myeloperoxidase levels (5 +/- 1; sham: 2 +/- 1 mU/ml) in bronchoalveolar lavage (BAL). Pretreatment with MnTBAP at a dose that prevented UAP-induced increases in oxidants effectively prevented increase in BAL cells (2.7 +/- 0.6 x 10(6), p < .0001 vs. UAP), PMN influx into the lungs (4 +/- 3%, p < .0001 vs. UAP), and increase in myeloperoxidase (2 +/- 1 mU/ml) and protein levels in BAL (0.1 +/- 0.1 mg/ml). These data indicate that superoxide anion is a critical mediator of the inflammatory response elicited by PM deposition in the lung.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Claudia Ramos
authors.initials: CR
authors.lastname: Rhoden
authors.forename: Elisa
authors.initials: E
authors.lastname: Ghelfi
authors.forename: Beatriz
authors.initials: B
authors.lastname: González-Flecha
mesh_terms: D000818:Animals; D005609:Free Radicals / Q000009:adverse effects / Q000378:metabolism; D008297:Male; D052638:Particulate Matter / Q000009:adverse effects / Q000378:metabolism*; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000009:adverse effects / Q000378:metabolism*
chemical_list: D005609:Free Radicals; D052638:Particulate Matter; D013481:Superoxides