Alterations in mast cells showing tryptase and chymase activity in epithelializating and chronic wounds

Mast cells can be found in contact with epidermis in certain circumstances; especially in chronic inflammatory skin diseases and chronic ulcers, but the significance of this association is obscure. In this study, the association of mast cells with wound healing was studied by counting mast cells in the wound edges at different stages after wounding the donor site skin for pinch-grafting. Chronic venous leg ulcers were biopsed for comparison. Tryptase- and chymase-positive mast cells were stained enzyme-histochemically for active proteinases. Both the number of tryptase-positive, i.e. total mast cells, and chymase-positive mast cells decreased during wound healing, but only the change in chymase-positive mast cells was statistically significant (P< or =0.03) the maximal decrease being 63% on day 7. No mast cells could be found in the vicinity of epithelialization margin. In venous leg ulcers, significantly more mast cells were present in the perilesional skin near the epithelium margin than in the wound bed (P=0.03), and mast cells were also seen in close contact with the basement membrane. Immunoreactivity for IL-4 and TNF-alpha in mast cells was studied to see if either of these molecules was associated with wound healing. In normally healing wounds, only a minority of mast cells were immunoreactive for these cytokines and no change in positive mast cell numbers could be seen during wound healing. In chronic wounds, IL-4 was absent in mast cells, and TNF-alpha positive mast cells were present only in perilesional skin and in small numbers. These results show that mast cells especially chymase-positive - decrease in number and can not be found in the epithelialization zone in normal wound healing, whereas tryptase-positive mast cells are associated with delayed wound healing and epithelialization in chronic wounds. Thus it seems, that mast cells attempt to control hyperproliferation of epidermis in chronic wounds.