Antigen Sensitization Influences Organophosphorus Pesticide–Induced Airway Hyperreactivity
http://www.ehponline.org/members/2008/10694/10694.html
Becky J. Proskocil,1 Donald A. Bruun,2 Jesse K. Lorton,1 Kirsten C. Blensly,1 David B. Jacoby,1,3 Pamela J. Lein,2 and Allison D. Fryer1
1Department of Physiology and Pharmacology, 2Center for Research on Occupational and Environmental Toxicology, and 3Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, USA
Abstract
Background: Recent epidemiologic studies have identified organophosphorus pesticides (OPs) as environmental factors potentially contributing to the increase in asthma prevalence over the last 25 years. In support of this hypothesis, we have demonstrated that environmentally relevant concentrations of OPs induce airway hyperreactivity in guinea pigs.
Objectives: Sensitization to allergen is a significant contributing factor in asthma, and we have shown that sensitization changes virus-induced airway hyperreactivity from an eosinophil-independent mechanism to one mediated by eosinophils. Here, we determine whether sensitization similarly influences OP-induced airway hyperreactivity.
Methods: Nonsensitized and ovalbumin-sensitized guinea pigs were injected subcutaneously with the OP parathion (0.001–1.0 mg/kg) . Twenty-four hours later, animals were anesthetized and ventilated, and bronchoconstriction was measured in response to either vagal stimulation or intravenous acetylcholine. Inflammatory cells and acetylcholinesterase activity were assessed in tissues collected immediately after physiologic measurements.
Results: Ovalbumin sensitization decreased the threshold dose for parathion-induced airway hyperreactivity and exacerbated parathion effects on vagally induced bronchoconstriction. Pretreatment with antibody to interleukin (IL) -5 prevented parathion-induced hyperreactivity in sensitized but not in nonsensitized guinea pigs. Parathion did not increase the number of eosinophils in airways or the number of eosinophils associated with airway nerves nor did it alter eosinophil activation as assessed by major basic protein deposition.
Conclusions: Antigen sensitization increases vulnerability to parathion-induced airway hyperreactivity and changes the mechanism to one that is dependent on IL-5. Because sensitization to allergens is characteristic of 50% of the general population and 80% of asthmatics (including children) , these findings have significant implications for OP risk assessment, intervention, and treatment strategies.
Key words: airway hyperreactivity, asthma, atopy, eosinophils, organophosphorus pesticides, parathion, sensitization. Environ Health Perspect 116:381–388 (2008) . doi:10.1289/ehp.10694 available via http://dx.doi.org/ [Online 2 January 2008]
