title: The influence of sensitization on mechanisms of organophosphorus pesticide-induced airway hyperreactivity.
abstract: We previously demonstrated that antigen sensitization increases vulnerability to airway hyperreactivity induced by the organophosphorus pesticide (OP) parathion. Sensitization also changes the mechanism of parathion-induced airway hyperreactivity to one that is dependent on IL-5. To determine whether this effect can be generalized to other OPs, and to other classes of pesticides, we measured airway responsiveness to vagal stimulation or intravenous acetylcholine in nonsensitized and ovalbumin-sensitized guinea pigs 24 hours after a single subcutaneous injection of the OPs diazinon or chlorpyrifos, or the pyrethroid permethrin. Sensitization exacerbated the effects of chlorpyrifos on bronchoconstriction in response to vagal stimulation or intravenous acetylcholine. Pretreatment with function-blocking IL-5 antibody prevented chlorpyrifos-induced airway hyperreactivity in sensitized, but not in nonsensitized, guinea pigs. In sensitized guinea pigs, blocking IL-5 decreased eosinophil activation, as measured by decreased eosinophil major basic protein in the trachea. In contrast, sensitization did not alter diazinon-induced airway hyperreactivity, and permethrin did not cause airway hyperreactivity in either nonsensitized or sensitized guinea pigs. None of the pesticides affected inflammatory cells in the bronchoalveolar lavage fluid or blood. We have previously shown that three different OPs cause airway hyperreactivity via loss of neuronal M2 muscarinic receptor function. Similar to parathion, but unlike diazinon, the mechanism of chlorpyrifos-induced airway hyperreactivity is changed by sensitization. Thus, OP-induced airway hyperreactivity is dependent on sensitization status and on the OP used, which may influence therapeutic approaches.
authors.affiliation: 1 Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon; and.
authors.forename: Becky J
authors.identifier: http://orcid.org/0000-0002-7803-6447
authors.initials: BJ
authors.lastname: Proskocil
authors.affiliation: 2 Department of Molecular Biosciences, University of California School of Veterinary Medicine, Davis, California.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Bruun
authors.affiliation: 1 Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon; and.
authors.forename: Jasmine A
authors.initials: JA
authors.lastname: Garg
authors.affiliation: 1 Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon; and.
authors.forename: Chloe C
authors.initials: CC
authors.lastname: Villagomez
authors.affiliation: 1 Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon; and.
authors.forename: David B
authors.identifier: http://orcid.org/0000-0003-2195-9512
authors.initials: DB
authors.lastname: Jacoby
authors.affiliation: 2 Department of Molecular Biosciences, University of California School of Veterinary Medicine, Davis, California.
authors.forename: Pamela J
authors.identifier: http://orcid.org/0000-0001-7665-7584
authors.initials: PJ
authors.lastname: Lein
authors.affiliation: 1 Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon; and.
authors.forename: Allison D
authors.identifier: http://orcid.org/0000-0003-1712-9831
authors.initials: AD
authors.lastname: Fryer
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction / Q000187:drug effects* / Q000276:immunology; D004390:Chlorpyrifos / Q000494:pharmacology; D003976:Diazinon / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D007114:Immunization; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007306:Insecticides / Q000494:pharmacology*; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000494:pharmacology*; D026023:Permethrin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014630:Vagus Nerve / Q000187:drug effects / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D007306:Insecticides; D015848:Interleukin-5; D026023:Permethrin; D010047:Ovalbumin; D004390:Chlorpyrifos; D000109:Acetylcholine; D003976:Diazinon
keywords: airway hyperreactivity; eosinophils; organophosphorus pesticides; permethrin; sensitization