ANCHORAGE-INDEPENDENT COLONY GROWTH OF PULMONARY FIBROBLASTS DERIVED FROM FIBROTIC HUMAN LUNG-TISSUE

Fibroblast heterogeneity is known to exist in chronically inflamed tis sue such as pulmonary fibrosis (IPF) and scleroderma. We have previous ly shown differences in proliferation rates in primary lines and clone d lines of fibroblasts derived from IPF tissue compared with normal lu ng. In this study, we report that cell lines derived from fibrotic tis sue demonstrate anchorage-independent growth in soft agarose culture w hereas normal lung fibroblast lines do not. We also show that fibrobla st lines derived from neonatal lung tissue form colonies at about the same frequency as the fibrotic cells. Colonies from both fibrotic and neonatal. lines were shown to be positive for vimentin, laminin, fibro nectin, fibronectin receptor, beta-actin, and tropomyosin by immunohis tochemistry but were negative for desmin, keratin, Factor VIII, alpha- smooth muscle cell actin, and tenascin. Treatment with cytokines TGF-b eta and PDGF or with corticosteroid modified the colony-forming capaci ty of fibrotic and neonatal cell lines, however, none of these treatme nts induced normal lung cell lines to form colonies. The presence of c ells in adult fibrotic tissue with growth characteristics similar to t hose exhibited by neonatal cells is further evidence of fibroblast het erogeneity and suggests newly differentiated fibroblasts may be preval ent in fibrotic tissue and contribute directly to the matrix disorder seen in this disease.