title: Airway hyperresponsiveness caused by aerosol exposure to residual oil fly ash leachate in mice.
abstract: Particulate air pollution is associated with exacerbation of asthma and other respiratory disorders. This study sought to further characterize the pulmonary effects of residual oil fly ash (ROFA), an experimentally useful surrogate for combustion-derived particulates in ambient air. Mice were exposed to aerosols of the soluble leachate of residual oil fly ash (ROFA-s). Physiologic testing of airway function (non invasive plethysmography) showed increased Penh, an index of airway hyperresponsiveness (AHR), in a time- and dose-dependent manner after exposure to ROFA-s. BAL analysis showed a minor influx of neutrophils, which was maximal at 12 h after exposure and essentially resolved by the time point of maximal AHR (48 h after exposure). The AHR caused by ROFA-s was reproduced by a mixture of its major metal components (Ni, V, Zn, Co, Mn, Cu) but not by any individual metal alone. Systemic pretreatment of mice with the antioxidant dimethylthiourea abrogated ROFA-s-mediated AHR. Analysis of mice of varying ages showed that ROFA-s had no marked effect on airway responsiveness of 2-wk-old mice, in contrast to the AHR seen in 3- and 8-wk old mice. ROFA-s-mediated AHR was unchanged in neurokinin 1 receptor knockout mice and in mice treated with an neurokinin antagonist, arguing against a role for this mediator in ROFA-s-mediated effects. Data indicate that ROFA-s mediates AHR in mice through antioxidant-sensitive mechanisms that require multiple metal constituents. Maturational differences in susceptibility to ROFA-induced AHR may be useful for further studies of mechanisms of particle effects.
authors.affiliation: Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Hamada
authors.forename: Carroll-Ann
authors.initials: CA
authors.lastname: Goldsmith
authors.forename: Yasue
authors.initials: Y
authors.lastname: Suzaki
authors.forename: Alejandra
authors.initials: A
authors.lastname: Goldman
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
mesh_terms: D000336:Aerosols; D000393:Air Pollutants / Q000009:adverse effects* / Q000276:immunology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology; D017745:Incineration; D007220:Industrial Waste; D007249:Inflammation; D019570:Inhalation Exposure; D019216:Metals, Heavy / Q000009:adverse effects*; D051379:Mice; D018345:Mice, Knockout; D009821:Oils; D012140:Respiratory Tract Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology
chemical_list: D000336:Aerosols; D000393:Air Pollutants; D000975:Antioxidants; D016207:Cytokines; D007220:Industrial Waste; D019216:Metals, Heavy; D009821:Oils