Altered Expression of Mast Cell Chymase and Tryptase and of c-Kit in Human Cutaneous Scar Tissue

Abstract

In order to explore a possible involvement of mast cells during human wound healing, we studied sections from scars (4-369-d-old) (N = 20) and normal skin (N = 10) for mast-cell-specific tryptase and chymase by enzyme histochemistry, for the stem cell factor receptor c-Kit and the melanosomal marker TA99 by immunohistochemistry, and for simultaneous c-Kit expression and avidin fluorescence by double staining. Enzyme activities and mRNA expression were also studied in tissue extracts. Chymase-reactive mast cell numbers as well as chymase activity and mRNA expression were reduced in all scars, whereas overall numbers of tryptase-reactive cells did not differ from normal skin, although tryptase activity and mRNA expression were increased in scar extracts. In contrast, numbers of c-Kit positive cells were significantly increased in old scars, and in the mid and lower dermis of all scars. A marked reduction of c-Kit reactivity was noted, however, in avidin-positive dermal mast cells and in epidermal basal cells, despite unchanged numbers of melanosome-positive cells, with an associated overall decrease of c-Kit mRNA in scar extracts. These data thus show that numbers of resident mast cells are very low in human cutaneous scars, suggesting massive mediator release from these cells into fresh wounds. Downregulation of stem cell factor receptors may also prevent these cells from increasing in number even in old scars. Instead, scar tissue is populated by a mast cell subpopulation that is chymase-, avidin-, tryptase +, c-Kit +, reflecting most probably an increased immigration and/or proliferation of immature mast cells and their precursors.

Mast cell chymase promotes hypertrophic scar fibroblast proliferation and collagen synthesis by activating TGF‑β1/Smads signaling pathway

“…In the formation stage of hypertrophic scars, an increase in the mast cell number is positively correlated with the severity of fibrosis (17). Compared with normal skin, active transmitters associated with mast cells are significantly increased, suggesting that mast cells and their transmitters are key factors for promoting hypertrophic scar formation (17). Chymase secreted by mast cells participates in the formation of skin matrix (18,19).…”

Possible involvement of mast cells in collagen remodeling in the late phase of cutaneous wound healing in mice

“…In human cutaneous wound healing, enzyme histochemical staining studies revealed that the number of chymase-positive mast cells decreased at various points after wounding, but that of tryptase-positive mast cells was either unchanged or increased [14][15][16]. According to Hermes et al [17], both chymase activity and its mRNA expression decreased in human scar extracts, whereas those of tryptase increased between day 23 and day 56 after wounding. Thus, it could be speculated that the tryptase-positive and chymase-negative mast cells appear during cutaneous wound healing.…”

A Brief Exposure to Tryptase or Thrombin Potentiates Fibrocyte Differentiation in the Presence of Serum or Serum Amyloid P

“…Mast cells are found in both internal fibrotic lesions and sites of wound healing (35–37). Mast cells degranulate in response to external stimuli (37) to release, among other things, the protease tryptase (37–39).…”