1. The differentiation and function of myofibroblasts is regulated by mast cell mediators.
- Author
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Gailit J, Marchese MJ, Kew RR, and Gruber BL
- Subjects
- Actins metabolism, Cell Differentiation physiology, Cell Line, Collagen physiology, Fibroblasts drug effects, Histamine pharmacology, Humans, Muscle, Smooth drug effects, Organ Culture Techniques, Serine Endopeptidases pharmacology, Tryptases, Tumor Necrosis Factor-alpha pharmacology, Fibroblasts cytology, Fibroblasts physiology, Mast Cells physiology, Muscle, Smooth chemistry, Muscle, Smooth physiology
- Abstract
Myofibroblasts are fibroblasts that express certain features of smooth muscle differentiation. Increased numbers of myofibroblasts and mast cells are frequently found together in a wide variety of settings, such as normal wound repair and scleroderma skin, which suggests that mediators produced by the mast cells could play a role in the regulation of myofibroblast differentiation and function. We used a human mast cell line, HMC-1, to determine if mast cells can induce normal human dermal fibroblasts to differentiate into functional myofibroblasts in vitro. We monitored the differentiation process by assaying two properties of the myofibroblast phenotype: expression of alpha-smooth muscle actin and functional capacity to contract a collagen matrix. In both a simple coculture system and in a skin-equivalent culture system, HMC-1 cells induced alpha-smooth muscle actin expression by fibroblasts. HMC-1 cells also stimulated fibroblast contraction of collagen gels, and the relative amount of contraction was dependent upon the number of HMC-1 cells present. To characterize the individual contributions made by specific mast cell products, we examined the effects of histamine, tumor necrosis factor alpha, and tryptase. Histamine induced a clear increase in alpha-smooth muscle actin expression, but it did not appear to stimulate fibroblast contraction. Tumor necrosis factor alpha had no effect in either assay. Purified human tryptase induced alpha-smooth muscle actin expression, and blocking the proteolytic activity of tryptase with specific inhibitors reduced that response. Tryptase inhibitors also eliminated the ability of HMC-1 cells to stimulate fibroblast contraction, suggesting that tryptase secreted by the HMC-1 cells may be one of the active mast cell mediators.
- Published
- 2001
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