Surfactant Protein D (SP-D) is a collagenous carbohydrate binding protein that is synthesized and secreted into the pulmonary airspaces by type II and bronchiolar epithelial cells. Although the physiologic roles of this protein have not been established, there is circumstantial evidence that SP-D contributes to pulmonary host defense, and that it could also participate in the extracellular metabolism of pulmonary surfactant. Our previous studies have also shown that SP-D production increases abruptly during late fetal lung development, and that SP-D mRNA and protein are increased following certain forms of lung injury. Accordingly, the major objectives of this Project are to examine the regulation of SP-D production at the tissue, cell, and molecular level - including the regulation of SP-D expression during lung development and following lung injury. Specifically, we propose: to examine the mechanisms of increased SP-D expression and accumulation during fetal and post-natal lung development in the rat - in vivo and in lung organ culture; to examine the mechanisms of increased SP-D mRNA and protein accumulation in bleomycin- induced fibrosis in rats; and to study the effects of selected cytokines and other mediators on SP-D gene expression and protein accumulation in cultures of adult rat type II and Clara cells, and adult rat lung organ culture. These studies will provide important new information related to the regulation of SP-D production. They will also contribute to our understanding of development and regulation of surfactant proteins, of cytokine-mediated alterations in lung epithelial cell function, and of alterations in the airspace lining material that accompany certain forms of acute and chronic lung injury.
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