Abstract
Exposure to diesel exhaust particulate matter (DEP) exacerbates asthma. Likewise, similar effects have been reported with exposure to the oxidizing air pollutant ozone (O3). Since levels of both pollutants in ambient air tend to be simultaneously elevated, we investigated the possible synergistic effect of these agents on the exacerbation of allergic airways disease in mice. Male BALB/c mice were sensitized ip with ovalbumin (Ova) or vehicle only, then exposed once per week for 4 wk via nose-only inhalation (4 h) to the PM2.5 fraction of DEP (2 mg/m3), O3 (0.5 ppm), DEP and O3, or filtered air, and then challenged with aerosolized ovalbumin. Ova sensitization in air-exposed mice enhanced pulmonary inflammatory cell infiltration, several indicators of injury in the lung (lactate dehydrogenase, albumin and total protein), and lung resistance (RL) and elastance (EL) in response to methacholine (MCh) aerosol challenge. DEP exposure did not enhance the Ova-induced increase in pulmonary cell infiltration, indicators of injury, or RL and EL. O3 exposure enhanced the Ova-induced increase in inflammatory cell infiltration and N-acetylglucosaminidase (NAG) in the lung, but had no effect on RL or EL. DEP co-exposure significantly attenuated the O3-induced increase in cell infiltration and indicators of injury; co-exposure had no effect on EL relative to air-exposed Ova-sensitized mice. However, only DEP-O3 co-exposure significantly increased the Ova-induced increase in RL. Thus, O3 and DEP co-exposure exacerbated airways hyperresponsiveness, a response that was not associated with parallel increases in pulmonary inflammation and one that may be mediated by a unique mechanism.
Acknowledgements
This article has been reviewed and approved for release by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency. Approval does not signify that the contents necessarily reflect the views and policies of the U.S. EPA, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The authors thank the following colleagues of the U.S. EPA: James R. Lehmann for his excellent technical assistance and thorough prepublication review of the article, Judy Richards and Paul Evansky for their excellent technical assistance, and Dr. Mehdi S. Hazari and Dr. Daniel L. Costa for their prepublication review of the article.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.