title: The differentiation and function of myofibroblasts is regulated by mast cell mediators.
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.
authors.affiliation: Department of Veterans Affairs Medical Center, Northport, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gailit
authors.forename: M J
authors.initials: MJ
authors.lastname: Marchese
authors.forename: R R
authors.initials: RR
authors.lastname: Kew
authors.forename: B L
authors.initials: BL
authors.lastname: Gruber
mesh_terms: D000199:Actins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D003094:Collagen / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008407:Mast Cells / Q000502:physiology*; D009130:Muscle, Smooth / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D012697:Serine Endopeptidases / Q000494:pharmacology; D053802:Tryptases; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000199:Actins; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine; D003094:Collagen; D012697:Serine Endopeptidases; D053802:Tryptases