The goal of this proposal is to determine the roles of alveolar macrophages (AM) and polymorphonuclear leukocytes (PMN) in the development of emphysema. RATIONALE: Emphysema is an important clinical problem. The mechanisms responsible for the development of emphysema are not known. However, it is known that: 1) Phagocytes are strategically located at the site of the primary lesions of emphysema, 2) Phagocytes produce enzymes and reactive oxygen species that can cause tissue destruction and 3) Cigarette smoking appears to alter the numbers and activities of AM and PMN in such a way to increase their potential toxicity for lung tissue. Hypothesis: The working hypothesis is that AM and/or PMN release proteolytic enzymes and reactive O2 species which participate in the development of emphysema. RESEARCH PLAN: A model of emphysema has been developed which involves intratracheal administration of CdCL2 to hamsters fed the lathyrogen Beta-adminoproprionitrile. Using this model, experiments have been designed that will: 1) Determine the time course relationships between the number of AM and/or PMN in the lung, their metabolic and enzymatic activities and the development of emphysema and 2) To determine the effect of selective depletion of AM and/or PMN on the development of emphysema. SIGNIFICANCE: The findings of the proposed research will provide a better understanding of lung injury so that methods of interrupting the process can be designed and tested.
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