Effect of heparin on pulmonary fibroblasts and vascular cells.

BACKGROUND: There is a large increase in mast cell numbers in fibrotic lung tissue, suggesting that mast cells may play a part in the pathogenesis of pulmonary fibrosis. Glycosaminoglycans, such as heparan sulphate, that are structurally related to heparin (a mast cell product) are part of the extracellular matrix and known to regulate cell growth. Basic fibroblast growth factor is a heparin binding growth factor produced by endothelial cells. METHODS: A study was carried out to examine the effect of heparin, basic fibroblast growth factor, and mast cell products on the proliferation of normal human lung fibroblasts and the effect of adding heparin on the proliferation of lung fibroblasts and pulmonary vascular cells incubated with basic fibroblast growth factor. RESULTS: Heparin at low concentration (0.03, 0.3-1.0 micrograms/ml) stimulated the proliferation of normal human lung fibroblasts in culture whereas a higher concentration (100 micrograms/ml) had an inhibitory effect. Mast cell products also stimulated the proliferation of fibroblasts, and the effect was decreased by pretreatment with heparinase or protamine. Heparin enhanced the growth of both fibroblasts and pulmonary vascular cells induced by low concentrations of basic fibroblast growth factor. CONCLUSIONS: Mast cells in fibrotic lung tissue may regulate fibroblast proliferation by releasing heparin. These results suggest that endothelial cells may interact with mast cells and modulate fibroblast growth by release of basic fibroblast growth factor.