Date of Award
Doctor of Philosophy (PhD)
Physiology and Pharmacology
The pathogenesis of airway hyperresponsiveness, a characteristic feature of asthma, is uncertain. Current evidence suggests a pathogenic role for immature (progenitors) and mature inflammatory cells, particularly eosinophils. The aim of this thesis was to examine the role of eosinophils and bone marrow progenitors in the development of allergen-induced airway hyperresponsiveness in dogs. Random source mongrel dogs demonstrating skin test reactivity to Ascaris suum allergen were studied. Acetylcholine airway responsiveness was measured before and 24 hours after inhalation of Ascaris allergen. For the second and third studies, dogs were pre-treated with inhaled budesonide twice daily for one week prior to allergen challenge. Airway eosinophils were enumerated from bronchoalveolar lavage samples and eosinophil activation was assessed by measurement of eosinophil peroxidase levels in bronchoalveolar lavage fluid. Bone marrow was obtained 24 hours after allergen inhalation with progenitors counted after 8 days in culture. In the first study, dogs that developed airway hyperresponsiveness were found to have a greater number of and more activated airway eosinophils before allergen inhalation than dogs that did not develop airway hyperresponsiveness. In the second study, pre-treatment with inhaled budesonide reduced the number of eosinophils present in the airways before allergen inhalation. This reduction was associated with an attenuation of allergen-induced airway hyperresponsiveness. In the third study, allergen inhalation increased bone marrow progenitor production in dogs that developed allergen-induced airway hyperresponsiveness. Furthermore, the increases in progenitors and airway hyperresponsiveness were reduced by pre-treatment with inhaled budesonide. These results suggest that pre-existing airway eosinophilia influences the development of airway hyperresponsiveness after allergen inhalation. In addition, the results from this thesis provide the first direct evidence that allergen inhalation can increase bone marrow progenitor production and suggest that such increases may contribute to the development of airway hyperresponsiveness in asthma.
Woolley, Mark J., "Eosinophils and bone marrow progenitors in allergen-induced airway hyperresponsiveness in dogs" (1993). Open Access Dissertations and Theses. Paper 3892.