Chronic allergic asthma is a complex syndrome characterized by hyperreactive airways and excess mucous production. However, aeroallergen bronchoprovocation of sensitized individuals may often be defined by an early and late phase asthmatic response (LAR). The pathophysiology of chronic or severe asthma may best be explained by the LAR. We have recently developed a model for allergen-specific early and late phase airway responses (LPR) in sensitized rabbits. This model closely simulates bronchoprovocation in human allergic subjects. During the LPR, rabbits develop airway obstruction and excess pulmonary secretions, rhonchi, and wheezes. We propose to utilize the model to specifically study the LPR in relation to non-specific bronchial hyperresponsiveness, pulmonary physiology, and histopathology using light and electron microscopy. We will also identify, isolate, and purify chemotactic factors for neutrophils and eosinophils released during the early and late phase responses. Litter-mates of New Zealand white rabbits will be immunized i.p. or by aerosol weekly with ragweed extract or fluorisceinated-ovalbumin from the day of birth, and control members of the litter will be sham-immunized. Sensitized rabbits, which make isotype specific IgE responses to allergen, and controls will be challenged with allergen, and their pulmonary responses recorded using standard techniques and oscillatory methods. Broncho-alveolar lavage (BAL) of challenged lungs will be performed sequentially and cells and tissue will be examined by light and electron microscopy. Sequential studies of BAL and serum will be performed to determine changes in allergen-specific IgG, A, and M with the amplified-ELISA and IgE with homologous PCA titers. Sequential samples of blood and lavage obtained during early and late phase responses will be analyzed for the presence of histamine using the redioenzyme method, and neutrophil and eosinophil chemotactic factors using Boyden chambers. If identified, these factors will be isolated and purified from lavage and serum using standard separation techniques and HPLC. This model of the early and late phase of allergen-induced airway reponses in an animal model for human asthma will be useful for testing new anti-asthmatic drugs, and understanding the requirements for certain cells, mediators, and inflammatory responses necessary for chronic or severe allergic asthma.
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