Mast Cells in Cutaneous Wound Healing

Mast cells are suggested to participate in wound healing, but their specific role has remained obscure. Mast cells are a rich source of inflammatory mediators, such as histamine, proteoglycans, the proteases tryptase and chymase, lipids, growth factors and cytokines. Among these mediators, there are many that have effects on cell growth, tissue turnover and repair. The aim of this study was to characterize the functions of mast cells in wound healing by studying mast cell activation in normal skin and the alterations undergone by mast cells in normally healing wounds, and investigating the effects of mast cell mediators on cultured keratinocytes and on epithelialization in vitro. The potential roles of mast cells and their mediators were explored also in chronic leg ulcers. The microdialysis technique was used to monitor histamine release in skin following skin challenge with neuropeptides substance P (SP), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), and capsaicin. SP and VIP, but not CGRP, caused mast cell degranulation and histamine release. Capsaicin, a neuropeptide releasing agent, did not cause any substantial histamine release, suggesting infrequent morphological contacts between mast cells and sensory nerves in normal human skin. In normally healing wounds, the numbers of mast cells, especially those with chymase activity, decreased in number and could not be found in the epithelialization margin. In chronic ulcers, mast cells were numerous in the perilesional skin and often in contact with the epithelial margin, and chymase was partially inactivated, as detected enzymeand immunohistochemically. The expression of stem cell factor (SCF, a mast cell growth factor) and Kit (its receptor on mast cells) showed significant alterations during wound healing. The numbers of dermal cells expressing SCF were markedly increased on day 1 after wounding and declined thereafter, whereas the expression of Kit increased steadily throughout wound healing. In chronic ulcers, most of the mast cells were Kit-positive, while SCF-positive cells were numerous in the wound bed. Thus, in chronic ulcers, there seems to be a potential for interaction between SCF and the Kit receptor, leading to mast cell proliferation, migration and degranulation. In contrast, only temporary SCFmediated mast cell activation seems to occur during normal wound healing. Maria Huttunen defended her thesis on December the 12th, 2003, in the Faculty of Medicine of the University of Kuopio. Faculty opponent was Professor Aarne Oikarinen (right), Department of Dermatology, University of Oulu, Finland and chairman was Professor Ilkka Harvima (left), Department of Dermatology, University