Pulmonary fibrosis results from an altered deposition of collagen within the lung parenchyma. This alteration is likely the result of both increased fibroblast proliferation and abnormalities in fibroblast collagen metabolism. Although the development of pulmonary fibrosis is preceded by inflammatory events in the lung, it is unclear whether altered fibroblast behavior requires continuous exposure to inflammatory mediators or alternatively results from the emergence in the lung of fibroblast populations possessing characteristics such as to explain the abnormalities seen in pulmonary fibrosis. To examine the latter hypothesis, we have established a number of fibroblast cell lines from control (C) lung tissue as well as from tissue from patients with active pulmonary fibrosis (PF), and have examined their in vitro proliferative characteristics. Our data show that PF fibroblasts proliferate significantly faster compared to C fibroblasts under standard culture conditions. We have also examined the in vitro proliferative characteristics of a substantial number of clonally derived fibroblasts. We report that a marked heterogeneity exists in terms of proliferation and also that a small but significant number of fast-growing clones are present in panels of clones derived from fibrotic tissue. These data suggest that there exists in fibrotic tissue, clones of fibroblasts with intrinsic growth characteristics which could in itself explain the increased fibroblast proliferation seen in pulmonary fibrosis. The fibrotic clones may emerge as dominant in the fibrotic lung under conditions of injury and repair likely to favor the expansion of this phenotype.

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In surgically excised nasal polyps, most epithelial mast cells were formalin sensitive, chloroacetate esterase (CAE) negative, and chymase negative. Thus, this represents a population of mast cells not identified by staining for CAE. On the other hand, most stromal mast cells were formalin resistant and CAE positive, and although there was some polyp-to-polyp variability in their content of neutral protease, most of these cells were positive for both tryptase and chymase. The percentage of metachromatic cells in the epithelium and the number of metachromatic cells per unit area of polyp tissue did not correlate with an index of allergy skin test reactivity or the serum IgE concentration. The percentage of mast cells surrounded by pericellular tryptase, suggesting activation/degranulation, was significantly higher in the stroma than in the epithelium. The findings demonstrate differences between the stroma and the epithelium in phenotype and state of activation of mast cells; these are postulated to be due to distinct microenvironmental factors that affect mast cells at these sites.