The production of collagen and the activity of mast‐cell chymase increase in human skin after irradiation therapy

Abstract

Fibrosis is a common complication of radiotherapy. The pathogenesis of radiation-induced fibrosis is not known in detail. There is increasing evidence to suggest that mast cells contribute to various fibrotic conditions. Several mast-cell mediators have been proposed to have a role in fibrogenesis. Tryptase and chymase, the predominant proteins in mast cells, have been shown to induce fibroblast proliferation and collagen synthesis in vitro. In order to explore the role of mast cells in irradiation-induced fibrosis, we analyzed skin biopsies and suction blister fluid (SBF) samples from the lesional and healthy-looking skin of 10 patients who had been treated for breast cancer with surgery and radiotherapy. The biopsies were analyzed histochemically for mast-cell tryptase, chymase, kit receptor, and tumor necrosis factor-alpha. Skin collagen synthesis was assessed by determining the levels of type I and III procollagen amino-terminal propeptides (PINP and PIIINP) in SBF and using immunohistochemical staining for PINP. Immunohistochemical stainings for prolyl-4-hydroxylase reflecting collagen synthesis and chymase immunoreactivity in irradiated and control skin were also performed. The mean level of procollagen propeptides in SBF, which reflects actual skin collagen synthesis in vivo, was markedly increased in irradiated skin compared to corresponding healthy control skin areas. The mean number of PINP-positive fibroblasts was also significantly increased in the upper dermis of radiotherapy-treated skin. The number of cells positive for tryptase, chymase and kit receptor was markedly increased in irradiated skin. In addition, using double-staining techniques, it was possible to demonstrate that in some areas of the dermis, tryptase-positive mast cells and fibroblasts are closely associated. These findings suggest a possible role of mast cells in enhanced skin collagen synthesis and fibrosis induced by radiotherapy.

Comparative study of mast cell count in oral reactive lesions and its association with inflammation

“…This process can be a result of the release of a series of fibrogenic cytokines such as platelet derived growth factor (PDGF), tumor necrosis factor (TnF-α) and basic fibroblast growth factor (b-FGF). In addition, the main components in mast cell granules are the tryptase and chymase enzymes that have been proven to stimulate and induce the proliferation of fibroblasts and type 1 collagen synthesis (3,12).…”

Comparison between the collagen intensity and mast cell density in the lingual muscles and myocardium of autopsied chronic chagasic and nonchagasic patients

“…Thus, although no published studies that compared changes in the tongue with changes in the heart of CD were found, we believed that in the cases analyzed, the tongue lesions caused by T. cruzi were older than the cardiac lesions and were at a more advanced stage of the tissue repair process, justifying the greater collagen density in the lingual muscles of Correlation between collagen intensity and MCH density in the myocardium of the chagasic patient group the chagasic patient group. Moreover, as a higher MCT density was found in lingual muscles than in the myocardium, we believed that these cells could have contributed to the fibrogenesis in the inflammatory process, since there is a study showing that tryptase-positive mast cells and fibroblasts are closely associated (Riekki et al 2004).…”

Fibrous Epulis Misdiagnosed for Combined Periodontic-Endodontic Lesion

“…[33] This was attributed due to the presence of a number of chemical mediators including histamines, proteases, chymase and tryptase within the secretory granules of the mast cells. [34,35,36] In addition to the above, mast cells were associated with increased migration and proliferation of fibroblasts [37] as well as affecting the fibroblast's functional behaviour through releasing fibrogenic cytokines including platelet-derived growth factor (PDGF), tumor necrosis factor-a (TNF-a), and basic fibroblast growth factor (b-FGF). [38,39] The last (b-FGF) was specifically associated with epulis formation.…”