Tissue Remodeling Fibrosis

Mast cells are increased in numbers in many fibrotic diseases and may play a crucial role in the development of fibrosis (101). The percentages of mast cells in bronchoalveolar lavage fluid from patients with sarcoidosis or intersti tial fibrosis are greater than from control individuals (102), and patients with idiopathic interstitial pulmonary fibrosis show evidence of mast cell degranulation and elevated mast cell numbers (103). In the kidney tissue of patients with IgA nephropathy, mast cell numbers correlate with the degree of interstitial fibrosis and creatinine clearance. In these kidney tissues, mast cells express tryptase and bFGF (104), which may be partially responsible for the fibrosis observed. The mast cell appears to be the dominant source of bFGF in some patients with pulmonary fibrosis (105). Similarly, patients with pulmonary fibrosis associated with scleroderma show higher numbers of mast cells and quantities of histamine and tryptase in bronchoalveolar lavage fluid than patients with normal chest roentgenograms (106). Mast cells also are found in intimate contact with myofibroblasts in keloid scars, suggesting they may play a role in fibroblast activation and scar formation (107). Thus, it appears that mast cells play a pivotal role in fibrotic disorders (108,109).

The mechanisms behind this relationship between mast cells and fibrosis/ tissue remodeling are unclear. Mast cell products, such as tryptase, TNF-a, and bFGF, induce fibroblast proliferation (105,110,111). However, fibroblasts appear to enhance mast cell survival, suggesting the presence of a bidirectional relationship between these cell types (3,112). Fibroblast expression of SCF and its interactions with c-kit on mast cells may provide one explanation for these observations. Fibroblasts, however, also are closely opposed to mast cells in fibrotic diseases, suggesting the additional possibility of cognate, cell-cell interaction such as that mediated by CD40-CD40L ligation (113,114). To further complicate the picture, mast cells are themselves capable of laying down some forms of collagen and mast cell tryptase can activate collagenases capable of matrix degradation. These data suggest multiple mechanisms by which and multiple levels where mast cells can regulate tissue fibrosis and repair (115).

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How To Reduce Acne Scarring

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