ALVEOLAR MACROPHAGE RESPONSE TO CHRONIC STIMULATION

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Chronic pulmonary infection with Pseudomonas aeruginosa, and associated airway obstruction are major factors in the pathophysiology of cystic fibrosis (CF). The high frequency of infection with a normally non-pathogenic organism has not been explained. Because of the difficulty in obtaining repeated lung lavage material from diseased patients, sequential studies have not been carried out on the humoral and cellular responses to chronic stimulation. To provide an experimental approach for such sequential analysis, we have adapted the agarose bead method of inducing chroninic pseudomonas pulmonary infection to the cat. A distinct advantage in using the cat is the size of the animal, allowing sequential sampling by bronchial lavage. This model has demonstrated similarities to CF including pathological changes in the lung as well as acquisition of the pseudomonas specific phagocytic inhibitory activity previously demonstrated in CF patients. This proposal is designed to investigate systemic and pulmonary host response to chronic stimulation. The pulmonary inflammatory cell response will be quantified and alveolar macrophage morphology and function evaluated with reference to duration of exposure to pseudomonas organisms as compared to exposure to a chronic irritant (agarose beads). Immunoglobulins and pseudomonas exoproducts will be identified and quantified in bronchial washings from infected cats. Finally, a combination of biochemical and immunochemical techniques will be employed to purify and characterize the inhibitory from the serum of infected cats. In addition to investigating the host response to pseudomonas pulmonary infection, this model will provide a useful approach to answer questions on the sequential cellular response to chronic non-microbial stimulation.