Lung fibroblasts produce growth stimulatory activity for bronchial epithelial cells

Interaction between lung fibroblasts and airway epithelial cells may play an important role in lung morphogenesis and airway repair after injury. Even though many reports have suggested that mesenchymal fibroblasts have a growth stimulatory effect on surrounding epithelial cells, very few have attempted to confirm and characterize the growth stimulatory activity in isolated cell systems. We cultured human fetal lung (HFL-1) fibroblasts, harvested supernatant-conditioned media under serum-free conditions, and examined their growth stimulatory effect on bovine bronchial epithelial cells by a variety of techniques, including direct enumeration, thymidine uptake, and metaphase arrest. We also partially characterized the growth stimulatory activity and examined the effect of an inhibitor of DNA synthesis on its release. The results demonstrate that HLF-1 fibroblasts release growth stimulatory activity for bovine bronchial epithelial cells. This activity is nondialyzable, protease-sensitive, acid-stable, and lipid-inextractable and thus appears to have the property of protein; it may be produced by de novo synthesis. Molecular sieve chromatography on Sephadex G-75 indicates an approximate molecular mass of 6,000 D. This growth stimulatory activity is likely to play roles in lung morphogenesis and airway repair after injury.