Background: The major role of mast cells in wound healing process has not been identified. In this study, we used mast cell-deficient W/WV mice and their congenic control (+/+) mice to examine the role of mast cells in scald wound healing. Methods: The size of the scald wound, thickness of the dermis, collagen deposition, vascularization, number of mast cells and chymase activity were measured before and at 3, 7, 14 and 21 days after inducing scald injury. Results: Although the process of wound closure and re-epithelialization was not markedly different between W/WV mice and +/+ mice, the degree of fibrous proliferation at the wound edge and wound vascularization in the proliferative phase was significantly lower in W/WV mice than in +/+ mice, and no vascular regression in the late remodeling phase was observed in W/WV mice. Mast cells producing chymase, FGF2, TGF-β1 and VEGF were highly accumulated at the edge of scald wound in +/+ mice during the proliferative and remodeling phases at days 14 and 21. Chymase activity in the injured tissues of +/+ mice decreased in the acute phase, but recovered to no-injury level at days 14 and 21. The number of mast cells and chymase activity were very low in the injured tissues of W/WV mice throughout the experiment. Conclusions: Wound healing after skin scald injury was partially impaired in mast cell-deficient mice. Mast cells may contribute to the wound healing process, especially in the proliferative and remodeling phases after scald injury.

Keywords:
Angiogenesis, Chymase, Fibrosis, Remodeling, Transforming growth factor-β1
1.
Eming SA, Krieg T, Davidson JM: Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol 2007;127:514–525.
2.
Martin P, Leibovich SJ: Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol 2005;15:599–607.
3.
El Sayed SO, Dyson M: Responses of dermal mast cells to injury. J Anat 1993;182:369–376.
4.
Hebda PA, Collins MA, Tharp MD: Mast cell and myofibroblast in wound healing. Dermatol Clin 1993;11:685–696.
5.
Egozi EI, Ferreira AM, Burns AL, Gamelli RL, Dipietro LA: Mast cells modulate the inflammatory but not the proliferative response in healing wounds. Wound Repair Regen 2003;11:46–54.
6.
Weller K, Foitzik K, Paus R, Syska W, Maurer M: Mast cells are required for normal healing of skin wounds in mice. FASEB J 2006;20:2366–2368.
7.
Shiota N, Kakizoe E, Shimoura K, Tanaka T, Okunishi H: Effect of mast cell chymase inhibitor on the development of scleroderma in tight-skin mice. Br J Pharmacol 2005;145:424–431.
8.
Yoshida S, Flancbaum L, Fitzpatrick JC, Berg RA, Fisher H: Effects of compound 48/80 and exogenous histamine on wound healing in mice. Proc Soc Exp Biol Med 1989;191:90–92.
9.
Bairy KL, Rao CM, Ramesh KV, Kulkarni DR: Effect of histamine on wound healing. Indian J Physiol Pharmacol 1991;35:180–182.
10.
Iba Y, Shibata A, Kato M, Masukawa T: Possible involvement of mast cells in collagen remodeling in the late phase of cutaneous wound healing in mice. Int Immunopharmacol 2004;4:1873–1880.
11.
Galiano RD, Michaels J, Dobryansky M, Levine JP, Gurtner GC: Quantitative and reproducible murine model of excisional wound healing. Wound Repair Regen 2004;12:485–492.
12.
Persinger MA, Lepage P, Simard JP, Parker GH: Mast cell numbers in incisional wounds in rat skin as a function of distance, time and treatment. Br J Dermatol 1983;108:179–187.
13.
Nishikori Y, Kakizoe E, Kobayashi Y, Shimoura K, Okunishi H, Dekio S: Skin mast cell promotion of matrix remodeling in burn wound healing in mice: relevance of chymase. Arch Dermatol Res 1998;290:553–560.
14.
Fang KC, Wolters PJ, Steinhoff M, Bidgol A, Blount JL, Caughey GH: Mast cell expression of gelatinases A and B is regulated by kit ligand and TGF-beta. J Immunol 1999;162: 5528–5535.
15.
Symington FW: Lymphotoxin, tumor necrosis factor, and gamma interferon are cytostatic for normal human keratinocytes. J Invest Dermatol 1989;92:798–805.
16.
Pillai S, Gilliam L, Conrad HE, Holleran WM: Heparin and its non-anticoagulant analogues inhibit human keratinocyte growth without inducing differentiation. J Invest Dermatol 1994;103:647–650.
17.
Huttunen M, Hyttinen M, Nilsson G, Butterfield JH, Horsmanheimo M, Harvima IT: Inhibition of keratinocyte growth in cell culture and whole skin culture by mast cell mediators. Exp Dermatol 2001;10:184–192.
18.
Huttunen M, Harvima IT: Mast cell tryptase and chymase in chronic leg ulcers: chymase is potentially destructive to epithelium and is controlled by proteinase inhibitors. Br J Dermatol 2005;152:1149–1160.
19.
Schechter NM, Sprows JL, Schoenberger OL, Lazarus GS, Cooperman BS, Rubin H: Reaction of human skin chymotrypsin-like proteinase chymase with plasma proteinase inhibitors. J Biol Chem 1989;264:21308– 21315.
20.
Walter M, Sutton RM, Schechter NM: Highly efficient inhibition of human chymase by alpha(2)-macroglobulin. Arch Biochem Biophys 1999;368:276–284.
21.
Schaffer CJ, Reinisch L, Polis SL, Stricklin GP: Comparisons of wound healing among excisional, laser-created, and standard thermal burns in porcine wounds of equal depth. Wound Repair Regen 1997;5:52–61.
22.
Werner S, Grose R: Regulation of wound healing by growth factors and cytokines. Physiol Rev 2003;83:835–870.
23.
Beanes SR, Dang C, Soo C, Ting K: Skin repair and scar formation: the central role of TGF-beta. Expert Rev Mol Med 2003;5:1–22.
24.
Mustoe TA, Pierce GF, Thomason A, Gramates P, Sporn MB, Deuel TF: Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science 1987;237:1333–1336.
25.
Shah M, Foreman DM, Ferguson MW: Neutralising antibody to TGF-beta 1,2 reduces cutaneous scarring in adult rodents. J Cell Sci 1994;107:1137–1157.
26.
Brown RL, Ormsby I, Doetschman TC, Greenhalgh DG: Wound healing in the transforming growth factor-beta-deficient mouse. Wound Repair Regen 1995;3:25–36.
27.
Taipale J, Lohi J, Saarinen J, Kovanen PT, Keski-Oja J: Human mast cell chymase and leukocyte elastase release latent transforming growth factor-β1 from the extracellular matrix of cultured human epithelial and endothelial cells. J Biol Chem 1995;270:4689–4696.
28.
Lindstedt KA, Wang Y, Shiota N, Saarinen J, Hyytiainen M, Kokkonen JO, Keski-Oja J, Kovanen PT: Activation of paracrine TGF-beta1 signaling upon stimulation and degranulation of rat serosal mast cells: a novel function for chymase. FASEB J 2001;15:1377–1388.
29.
Moulin V: Growth factors in skin wound healing. Eur J Cell Biol 1995;68:1–7.
30.
Hiromatsu Y, Toda S: Mast cells and angiogenesis. Microsc Res Tech 2003;60:64–69.
31.
Noli C, Miolo A: The mast cell in wound healing. Vet Dermatol 2001;12:303–313.
32.
Bertolino P, Deckers M, Lebrin F, ten Dijke P: Transforming growth factor-beta signal transduction in angiogenesis and vascular disorders. Chest 2005;128(6 suppl):585S–590S.
33.
Galli SJ, Tsai M: Mast cells: versatile regulators of inflammation, tissue remodeling, host defense and homeostasis. J Dermatol Sci 2008;49:7–19.
34.
Peters EM, Maurer M, Botchkarev VA, Jensen K, Welker P, Scott GA, Paus R: Kit is expressed by epithelial cells in vivo. J Invest Dermatol 2003;121:976–984.
35.
Grimbaldeston MA, Chen CC, Piliponsky AM, Tsai M, Tam SY, Galli SJ: Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo. Am J Pathol 2005;167:835–848.
36.
Zhou JS, Xing W, Friend DS, Austen KF, Katz HR: Mast cell deficiency in Kit(W-sh) mice does not impair antibody-mediated arthritis. J Exp Med 2007;204:2797–2802.
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2009
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