MACROPHAGE INTERLEUKIN 1 PRODUCTION IN EVOLVING SILICOSIS

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Silicosis is a chronic inflammatory and fibrotic lung disease resulting from inhalation of crystalline forms of silicon dioxide. The investigations of this Project form an integrated, collaborative approach that will address several aspects of the events initiated by silica particle-lung cell interactions which then lead to injury, inflammation, and subsequent fibrosis. We hypothesize that the initial interactions of silicon dioxide particles with biological molecules and cells determine the degree and nature of the lung response, and that these interactions are primarily a function of specific particle surface properties. Subsequent events and the development of chronic lung pathology are determined both by the continued presence of particulates and by the functions of the inflammatory and immune cells recruited to the lung. This Project will focus on studies of cellular responses in the lungs of rats following exposure to silica. Our major goals are to assess the functions and interactions of pulmonary macrophages and lymphocytes in the evolution of silicosis in an animal model of aerosol exposure to two forms of silicon dioxide, cristobalite and quartz. These two forms of crystalline silicon dioxide are known to cause pulmonary disease in humans and experimental animals, but differ markedly in their degree of fibrogenicity. This project will study secretion by macrophages of interleukin-1, (IL-1) and suppressors which may counter balance its effects. The presence and function of specific cell types or subpopulations in the alveolar fluids will be related to the functions of other cells and correlated with the overall course of pulmonary disease. The role of cell mediated immune mechanisms in response to silica will be further investigated in a model utilizing exposure of T- lymphocyte deficient (athymic) strains of rats to cristobalite and quartz. Silicosis provides a model of chronic diffuse interstitial immunologic and fibrotic lung disease in which the cause is known. Further studies of silicosis will provide new insights into the mechanisms of this important occupational lung disease, better treatment for those who suffer from it, and better understanding of the mechanisms which govern pulmonary injury, inflammation, repair and fibrosis.