SYNTHESIS OF BASIC FIBROBLAST GROWTH-FACTOR BY MURINE MAST-CELLS - REGULATION BY TRANSFORMING-GROWTH-FACTOR-BETA, TUMOR-NECROSIS-FACTOR-ALPHA, AND STEM-CELL FACTOR

Background: Mast cells (MC) are involved in a wide spectrum of disorde rs characterized by neovascularization and fibroproliferation. We and others recently reported that human MC are a source of basic fibroblas t growth factor (b FGF-2), a potent angiogenic and mitogenic polypepti de, in several disease conditions, such as chronic inflammation, heman gioma, and benign cutaneous mastocytosis. These findings suggest that FGF-2 may be an important mediator of cell proliferation and angiogene sis associated with MC. Since MC are heterogeneous across species, it is unknown whether FGF-2 expression is a feature common to all MC, or whether FGF-2 expression by MC can be regulated. We therefore examined FGF-2 expression by MC in mouse tissue and MC lines. Methods: Immunos taining, RT-PCR, ELISA, immunoblot and Northern blot analyses were emp loyed to study four murine MC lines for FGF-2 expression and its regul ation by transforming growth factor-beta (TGF-beta), stem cell factor (SCF), and tumor necrosis factor-alpha (TNF-alpha). Results: Mouse tis sue MC and three of four murine MC lines (CFTL-12, CFTL-15, ABFTL-3) e xpress FGF-2 as judged by immunostaining, ELISA, Western blot and Nort hern blot analyses, and reverse transcription-polymerase chain reactio n. While TNF-alpha appeared to downregulate FGF-2 mRNA levels, treatme nt with SCF or TGF-beta resulted in an increase in the expression of F GF-2 at mRNA level which can be attenuated by TNF-alpha. However, the concurrent increase in FGF-2 protein was negligible, possibly due to i mmaturity of these cell lines. Conclusion: Expression of FGF-2 may be a ubiquitous feature of MC in other species in addition to humans, and can be selectively regulated by SCF, TGF-beta and TNF-alpha.