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A2213 - Pulmonary Fibrosis: The Alveolar Type I Cell Hypothesis
Author Block: R. J. Mason1, K. Correll1, R. Zemans2, E. F. Redente3; 1Medicine, National Jewish Health, Denver, CO, United States, 2Internal Med - Pulmonary, Univ of Michigan, Ann Arbor, MI, United States, 3Pediatrics, National Jewish Health, Denver, CO, United States.
Rationale. The one epithelial cell type that is missing in honeycomb cysts is the type I cell. Type I cells are very susceptible to injury and proliferate rarely, if at all. They can, however, spread and cover a large alveolar surface area. We hypothesize that type I cells limit fibroblast matrix production and their differentiation into myofibroblasts. Methods. We cultured human type II cells with or without human fibroblasts on a collagen coated surface with and without TGF beta. Results. Type II cells cultured on collagen lose their expression of the surfactant proteins and acquire the expression of some type I cell genes (EMP2 and RAGE). The two cell types were cultured alone or in co-culture in the presence or absence of TGF beta. The two cell types were re-isolated with EP-CAM magnetic beads at the end of the experiments. In the co-culture the two cell types self aggregated and the epithelial cells suppressed fibroblast expression of COL1A1 (type I collagen), ACTA2 (smooth muscle actin), CCN2 (connective tissue growth factor), and FN1 (fibronectin) as well as HGF (hepatocyte growth factor), FGF7 (fibroblast growth factor 7, KGF) and FGF10. The epithelial cells suppressed COL1A1, ACTA2, and CCN2 even in the presence of TGF beta. Conclusions. The implication is that type I cells actively suppress fibroblast gene expression and are likely critical for the restoration of alveolar units after lung injury. The epithelial defect in IPF should also include the loss of type I cells.