Human exposures to coal dust are associated with the development of Simple Coal-workers' Pneumoconiosis (CWP). Focal emphysema is a part of Simple CWP. This lesion has been ascribed to contraction of connective tissue fibers deposited in this locus with consequent enlargement of adjacent airspaces. Alternatively this lesion may result due to elastin lysis from elastolytic enzymes produced in either polymorpho-nuclear leukocytes and/or alveolar macrophages. The purpose of this proposal is to study the hypothesis that elastase and collagenase secreted by alveolar macrophages following in vivo exposure of laboratory animals to three major types of coal -- anthracite, bituminous and lignite -- will create focal emphysema and Simple CWP. The ability of macrophages which have phagocytized coal dust to produce and secrete enzymes in concentrations which exceed the capacity of natural protease inhibitors Alpha2-macroglobulin and alveolar alpha1-antitrypsin will be studied so as to evaluate the role of coal on protease-anti-protease balance. The effect of chronic coal dust exposure on the macrophage proteases and alveolar antiproteases will be studied by monitoring the total amount of these substances after repeated exposures to coal dust. This will be done by analyzing the alveolar lavage fluid for Alpha2-macroglobulin and Alpha1-antitrypsin and bronchial protease inhibitor by specific radioimmunoassay. Alveolar macrophage and alveolar neutrophil elastase and collagenase will also be studied. Phagocytosis of coal dust will generate superoxide ions and other oxygen metabolites. These substances have been observed to inhibit Alpha1-AT, the major antiprotease in the alveolar environment. We will study the extent of superoxide and oxygen metabolites generated by alveolar macrophages which have phagocytized coal dust and observe the effects on the alveolar antiproteases. Inhibition of the alveolar antiproteases will create a greater potential activity for the macrophage and neutrophil proteases and therefore encourage the development of focal emphysema. The effects of well recognized environmental pollutants such as nitrogen dioxide and cigarette smoke will be studied in conjunction with coal dust exposure in order to elucidate the effects on antiproteases and the balance of alveolar protease-antiprotease materials which may influence the development of focal emphysema of coal-workers' pneumoconiosis.
