Antigen Sensitization Influences Organophosphorus Pesticide-Induced Airway Hyperreactivity

• Published in: Environmental health perspectives Vol. 116; no. 3; pp. 381 - 388
• Main Authors: Proskocil, Becky J., Bruun, Donald A., Lorton, Jesse K., Blensly, Kirsten C., Jacoby, David B., Lein, Pamela J., Fryer, Allison D.
• Format: Journal Article
• Language: English
• Published: United States National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare 01.03.2008; National Institute of Environmental Health Sciences
• Subjects: Acetylcholinesterase - metabolism; Animals; Asthma; Bradycardia - chemically induced; Bradycardia - physiopathology; Bronchial Hyperreactivity - chemically induced; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - physiopathology; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Bronchoconstriction; Bronchoconstriction - drug effects; Chemical hazards; Dose-Response Relationship, Drug; Electric Stimulation; Eosinophils; Female; Guinea Pigs; Immunization; Interleukin-5 - immunology; Lungs; Muscarinic receptors; Nerves; Ovalbumin - immunology; Pain; Parathion - toxicity; Pesticides; Pesticides - toxicity; Sensitization; Vagus Nerve - physiopathology; airway hyperreactivity; parathion; atopy; organophosphorus pesticides; eosinophils; asthma; sensitization
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.10694

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.