Although the pathogenesis of lung injury is poorly understood, the proteinase-antiproteinase theory of lung injury suggests that the sparing or degredation of the alveolar connective tissue is due, at least in part to the balance between secretion of metalloproteinases and tissue inhibitor of metalloproteinase (TIMP) by alveolar and interstitial macrophages. This application proposes to determine the potential role of macrophage metalloproteinases and TIMP in the pathogenesis of acute and chronic lung disease. During the first year, she will compare, through the use of rodent models of reversible and irreversible lung injury, the ability of alveolar and interstitial macrophages to secrete specific metalloproteinases and TIMP. During the next two years, she will identify mediators that modulate the secretion of these macrophage secretory products in different disease states. In the final two years, she hopes to conduct independent research to determine how these mediators modulate the secretion of metalloproteinases and TIMP by macrophages.