LUNG COLLAGEN IN SILICOSIS: FIBROSIS MECHANISMS

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Previous studies of experimental pulmonary fibrosis induced in rodents by silica, bleomycin, ozone, or paraquat suggest that collagen metabolism in silicosis differs from collagen metabolism in other types of fibrosis. In this proposal I plan to investigate new aspects of collagen metabolism in silicosis. Specifically, I propose to conduct a detailed investigation of lung collagen crosslinking, using in vivo labeling coupled with a new HPLC technique, in three groups of rats: controls, rats exposed to silica, and rats exposed to bleomycin. Parameters to be examined include type and amount of crosslink per collagen molecule, time course of crosslink formation, turnover of crosslinks, reducibility of crosslinks, and location of crosslinks. I hypothesize that specific crosslinking patterns may act as a kind of signal, determining whether the collagen is destined to become irreversibly deposited as "fibrosis collagen" or whether it is eventually destined for degradation. I further hypothesize that lung collagen crosslinking in silicotic animals will differ from that found in both normal and bleomycin-exposed rats. Finally, I will use the data base derived from these studies to guide the development of simple urine screening assays indicative of early silicotic changes.