Pulmonary fibrosis is a disease of widespread occurrence and unknown cause. Despite its heterogenous nature it is likely that certain basic underlying processes at the molecular level are responsible for its pathogenesis. Progress has been slow towards our understanding of the cellular and molecular basis of pulmonary fibrosis largely on methodologic grounds, with most studies to date dealing with whole lung or heterogenous populations of lung cells and using methods which have not directly examined collagen synthesis. Important questions remain as to what specific cell types are involved in the disease process and as to whether fibrosis is caused by changes in connective tissue (collagen) quantity, quality or both. An exciting development in our understanding of pulmonary fibrosis is the evidence that the collagen types present are altered. The central hypothesis of the proposed research is that the cellular basis of pulmonary fibrosis is an altered phenotype of the lung fibroblast. We have established cultures of fibroblasts obtained by subsegmental lavage through the bronchofiberscope from patients with pulmonary fibrosis. We believe that these cells which can be isolated from 70 percent of fibrosis patients may have been directly involved in the fibrotic process in situ. They thus may offer a unique key to the cellular basis of pulmonary fibrosis. To quantitate collagen synthesis we will determine the fraction of protein synthesized by these cells which is collagenase-sensitive and compare them with established normal lung fibroblast strains. Major emphasis will be placed on quantitating Type I and Type III collagen synthesized by these cells, given the recent evidence that changes in collagen type ratios are important in fibrotic process. Such a phenotypic characterization should prove to be a powerful tool to further our understanding of the cellular basis of pulmonary fibrosis and lead to better diagnostic and therapeutic tools.
NIH ExPorter
NIH ExPorter