The Differentiation and Function of Myofibroblasts is Regulated by Mast Cell Mediators

• Published in: Journal of investigative dermatology Vol. 117; no. 5; pp. 1113 - 1119
• Main Authors: Gailit, James, Marchese, Mary J., Kew, Richard R., Gruber, Barry L.
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.11.2001; Nature Publishing; Elsevier Limited
• Subjects: Actins - metabolism; Biological and medical sciences; Cell Differentiation - physiology; Cell Line; collagen; Collagen - physiology; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - physiology; Fundamental and applied biological sciences. Psychology; histamine; Histamine - pharmacology; Humans; Mast Cells - physiology; Muscle, Smooth - chemistry; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Organ Culture Techniques; Serine Endopeptidases - pharmacology; transforming growth factor β; tryptase; Tryptases; Tumor Necrosis Factor-alpha - pharmacology; Vertebrates: skin, associated glands, phaneres, light organs, various exocrine glands (salt gland, uropygial gland...), adipose tissue, connective tissue; α-actin; collagen; histamine; α-actin; tryptase; transforming growth factor β; Human; Immunohistochemistry; Cell culture; Serine endopeptidases; Enzyme; Myofibroblast; Cell differentiation; In vitro; Functional capacity; Pathology; Peptidases; Connective tissue; Collagen; Tryptase; Hydrolases; Mast cell; Mediator; Skin; Molecular biology
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1046/j.1523-1747.2001.15211.x

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 α-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 α-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 α, and tryptase. Histamine induced a clear increase in α-smooth muscle actin expression, but it did not appear to stimulate fibroblast contraction. Tumor necrosis factor α had no effect in either assay. Purified human tryptase induced α-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.