An animal model for pulmonary hypersensitivity to airborne industrial chemicals has been developed using guinea pigs. Exposure conditions were designed to mimic those found in the industrial situation, i.e., exposure is via the inhalation route, animals are unrestrained being kept in whole body plethysmographs, assuring normal breathing patterns and thus normal distribution of chemical in the respiratory tract, and no immunologic adjuvants are used to artificially stimulate an immune response. Using the model, both immediate and late-onset pulmonary responses have been obtained to both an industrial protein allergen (subtilisin) and to a reactive industrial chemical, diphenylmethane diisocyanate (MDI). Further, the time of onset of the immediate and late-occurring reactions coincides with those reported for industrial workers. The objective of this proposal is to investigate the mechanism(s) of these pulmonary responses as well as of hypersensitivity pneumonitis. The hypothesis to be tested is that the ability of a sensitized animal to respond to inhalation challenge with specific allergen and display a pulmonary hypersensitivity reaction is dependent upon a combination of three factors: (a) airway hyperreactivity (b) specific cytophilic antibody (c) antigen-specific lymphocytes. Each of these components will be evaluated in inbred strain #2 guinea pigs sensitized to ovalbumin by inhalation exposure. Airway hyperreactivity will be artifically produced by exposure of animals to 1 ppm ozone. Hyperreactive airways will be assessed by dose-response reactions to increasing concentrations of carbamylcholine. Class-specific antibodies will be isolated by HPLC or affinity chromatography and antigen-specific lymphocytes by flow cytometry. Elucidation of the mechanism(s) underlying immediate- and late-onset pulmonary reactions, as well as hypersensitivity pneumonitis should enable recommendation of appropriate testing procedures to identify those sensitized individuals likely to experience adverse pulmonary hypersensitivity reactions.
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