Lung morphology and function are dependent on connective tissue which comprises nearly one-fourth of the lung tissue mass, and on collagen, which is its principal protein component. Abnormalities in the connective tissue component contribute to pulmonary dysfunction. A common disorder, fibrosis, results from diverse etiology, leading to generalized proliferation of connective tissue demonstrable by morphological criteria. Considerable investigative effort has been invested in the examination of histopathology and pulmonary physiology of fibrotic lungs; however, in the absence of background biochemical information, it has not been possible to correlate etiology with tissue response. A major handicap in elucidating the biochemical events leading to pulmonary fibrogenesis accrues from the complexity of systemic responses, e.g. immunological phenomena and infiltrating circulatory cells elicited by the fibrogenic stimulus. This problem can be circumvented by explant procedures; however, generation of biochemical responses requires changes at several levels of cellular regulation spread over a schedule longer than the viability of explants. We have developed an organ culture system capable of maintaining lung explants for a period of over five days, long enough for the observation of major biochemical changes, which in the intact animal, are apparent after 24 hours after exposure to certain toxins. This model system is eminently suitable for investigations on the cellular and molecular bases of fibrogenic responses to a variety of agents. We propose to use lung organ cultures, (1) to investigate the variety of collagen normally synthesized in the mammalian lungs, 2) to delineate qualitative and quantitative changes in collagen in the presence of fibrogenic stimuli and 3) to examine the cellular sites and molecular bases of the interactions of fibrogenic agents with lung connective tissues. BIBLIOGRAPHIC REFERENCES: Bhatnagar, R. S. and Hussain, M. Z., Lung organ cultures as model for pulmonary fibrotic diseases, Am. Thoracic Society Meeting, San Francisco, Am. Rev. Resp. Dis., 1977. Hussain, M. Z., Enriquez, B., Tolentino, M. and Bhatnagar, R. S., Stimulation of collagen and collagen-related tRNA levels in lung organ cultures, Fed. Proc. 38:607 (1977).
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