title: Antigen sensitization influences organophosphorus pesticide-induced airway hyperreactivity.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon 97239, USA. proskoci@ohsu.edu
authors.forename: Becky J
authors.initials: BJ
authors.lastname: Proskocil
authors.forename: Donald A
authors.initials: DA
authors.lastname: Bruun
authors.forename: Jesse K
authors.initials: JK
authors.lastname: Lorton
authors.forename: Kirsten C
authors.initials: KC
authors.lastname: Blensly
authors.forename: David B
authors.initials: DB
authors.lastname: Jacoby
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Lein
authors.forename: Allison D
authors.initials: AD
authors.lastname: Fryer
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007114:Immunization; D015848:Interleukin-5 / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology*; D010278:Parathion / Q000633:toxicity*; D010575:Pesticides / Q000633:toxicity*; D014630:Vagus Nerve / Q000503:physiopathology
chemical_list: D015848:Interleukin-5; D010575:Pesticides; D010278:Parathion; D010047:Ovalbumin; D000110:Acetylcholinesterase