title: Time Course of Eosinophilic Recruitment and Pulmonary Toxicity Biomarkers in an Allergic Asthma Model in Brown Norway Rats.
abstract: Allergic asthma is a pulmonary disease characterized by antigen-induced pulmonary eosinophilia, airway hyperresponsiveness, antigen-specific IgE antibody responses, and broncho-constriction. In attempting to elucidate mechanisms associated with the pathogenesis of this disease, a number of animal models have been developed. The current studies were undertaken to develop a model of allergic asthma model in Brown Norway rats. Unlike the neutrophilic inflammatory response to inhaled particles in most strains of rats, inhalation of antigens in sensitized Brown Norway rats results in a complex cellular response which is characterized by a variety of inflammatory cell types, and is dependent on the time course of inflammatory cell recruitment. In characterizing this ovalbumin-challenge model of allergic asthma, it was important to assess the time course of pulmonary inflammation, cell proliferation, and apoptosis. Male Brown Norway rats were sensitized and boosted with intraperitoneal injections of ovalbumin in aluminum hydroxide on experimental days 1 and 8. On days 15-17, rats were challenged by an inhalation exposure to 5% ovalbumin and were evaluated by bronchoalveolar lavage (BAL) at 24 or 48 h postexposure (PE). Control rats were similarly treated to ovalbumin aerosol exposures; however, these animals had been sensitized and boosted with aluminum hydroxide (minus the ovalbumin). Cell differential evaluations demonstrated that the rats exposed for 3 days/24 h postexposure and for 2 days/ 48 h postexposure produced the greatest numbers of BAL eosinophils and corresponding indicators of pulmonary toxicity. It was interesting to note that earlier exposure time periods (i.e., 1 day/24 h PE) generated a predominantly neutrophilic inflammatory response, while longer exposure/postexposure time periods (i.e., 3 days/48 h) produced a predominant mononuclear inflammatory response. Subsequent studies demonstrated that the 2-day/ 48-h protocol produced the optimum eosinophilic, cytotoxic, cell proliferative, and apoptotic response. Histopathological evaluations demonstrated a chronically active alveolitis and bronchiolitis, characterized by epithelial cell proliferation in the airways and inflammatory cell proliferation in the alveoli. Studies are ongoing to assess the cell types undergoing apoptosis in both the airway and parenchymal regions to fully characterize this model in order to assess its relevance and utility for studying asthma in humans.
authors.affiliation: a DuPont Haskell Laboratory , Newark , Delaware , USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Warheit
authors.affiliation: a DuPont Haskell Laboratory , Newark , Delaware , USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Webb
authors.affiliation: a DuPont Haskell Laboratory , Newark , Delaware , USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Reed