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Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure
Published on: August 25, 2017
A mechanism of synergistic lung damage by ozone and a respirable aerosol
Abstract:
A hitherto unexpected synergism between the oxidant air pollutants ozone or nitrogen dioxide and a respirable-sized aerosol of ammonium sulfate was previously observed during controlled exposures of rats to these substances. In this paper we examine biochemical and morphometric changes in lungs of rats exposed for 3, 7, or 14 days to ozone (0.64-0.96 ppm), with or without an accompanying aerosol (approximately 1 micrometer mass median aerodynamic diameter) of ammonium sulfate (5 mg/m3). After 3 days of exposure to the mixture of pollutants, rat lung macrophage and macrophage precursors (monocytes) were increased 2- to 3-fold, fibroblasts were increased 2-fold, and apparent collagen synthesis rates were increased 2.5-fold, fibroblasts were increased 2-fold, and apparent collagen synthesis rates were increased 2.5-fold, as compared with values from animals exposed to ozone alone. Continued exposure to ozone alone for 7 or 14 days seemed to mimic changes seen at 3 days with the mixture of pollutants. Total number of lesions per lung was the same for ozone exposure with and without accompanying aerosol; lesions were larger in lungs of rats exposed to ozone plus ammonium sulfate. Based on these findings and a review of the literature, a mechanism for ozone-aerosol synergism is proposed. We suggest that the lifetime of free radicals arising from interaction of oxidants such as ozone or nitrogen dioxide with molecules within the lung is increased by either local pH changes or changes in the local sulfate concentration (or both) caused by inhalation of the respirable aerosol.
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