MAST-CELLS ARE A MAJOR SOURCE OF BASIC FIBROBLAST GROWTH-FACTOR IN CHRONIC INFLAMMATION AND CUTANEOUS HEMANGIOMA

Mast cells play an essential role during development of inflammation a fter chemical and immunological insults and have been implicated in ti ssue fibrosis and angiogenesis. The exact contribution of mast cells t o these conditions is largely unknown. In this study, we found that a potent angiogenic and mitogenic polypeptide,basic fibroblast growth fa ctor (bFGF), is localized to the majority of mast cells from normal sk in and lung and in tissue sample characterized by fibrosis, hyperplasi a, and neovascularization. Using specific antibodies to mast cell tryp tase, tissue macrophage, and bFGF, we demonstrate that cytoplasmic bFG F immunoreactivity is localized to 96.8 +/- 9.6% of tryptase-positive cells in human fibrotic lung tissue (n = 10), 82.3 +/- 6.9% of tryptas e-positive cells in rheumatoid synovia (n = 6), and 93.1 +/- 4.8% of t ryptase-positive cells in skin hemangioma (n = 5). Moreover, these try ptase-positive comprise a major portion (86 to 97%) of nonvascular cel ls exhibiting cytoplasmic bFGF staining in these tissues. In contrast, macrophage-like cells contribute less than 10% of the bFGF-positive c ells in the same samples. The specificity of the immunostaining result s was supported by the finding that cultured human mast cells (HMC-1) express both bFGF mRNA and protein. Our data indicate that mast cells, a primary source of heparin, also serve as a significant source of a heparin-binding growth factor, bFGF, in these disease processes. These observations suggest that mast cells may contribute to these patholog ical conditions by releasing this polypeptide.