title: The role of mouse mast cell proteases in the proliferative phase of wound healing in microdeformational wound therapy.
abstract: BACKGROUND
  Stored in the secretory granules of cutaneous mouse mast cells are mouse mast cell proteases (mMCP-4, -5, and -6). Using transgenic mouse lines that lacked these enzymes, it was shown that mMCP-4 and mMCP-5 modulate the outcome of burn-induced skin injury. Whether or not these proteases also play a role in the repair of surgically damaged skin, with or without microdeformational wound therapy, remains to be determined.
  
  
  METHODS
  Wild-type C57BL/6 mice and transgenic C57BL/6 mouse lines lacking mMCP-4, -5, or -6 were subjected to surgical wounding of their skin. Wounds were splinted with a stabilizing patch, and the mice received either microdeformational wound therapy (n = 5) or occlusive dressing (n = 5) for 7 days. Wound healing parameters were assessed in the proliferative phase.
  
  
  RESULTS
  Cell proliferation in the wounded wild-type mice receiving microdeformational wound therapy was 60 ± 3 percent. Cell proliferation was only 35 ± 5 percent, 25 ± 5 percent, and 45 ± 4 percent for the treated mMCP-4-, mMCP-5-, and mMCP-6-null mice, respectively (p = 0.005). Blood vessel sprouting was higher in the control mice with microdeformational wound therapy (170 ± 40 vessels/high-power field) compared with mouse mast cell protease 6-null mice with microdeformational wound therapy (70 ± 20 vessels/high-power field; p = 0.005), and higher in the control mice with occlusive dressing (110 ± 30 vessels/high-power field) compared with mMCP-4-null mice with occlusive dressing (50 ± 20 vessels/high-power field; p = 0.01). Qualitatively, the granulation tissue of all the protease-deficient groups receiving microdeformational wound therapy was disrupted.
  
  
  CONCLUSIONS
  Results suggest that mouse mast cell proteases 4, 5, and 6 are mediators of the critical role mast cells play in microdeformational wound therapy in the proliferative phase of healing.
authors.affiliation: Lexington, Ky.; Baltimore, Md.; Padova, Italy; Shanghai, People's Republic of China; Ibaraki, Japan; Falls Church, Va.; Uppsala, Sweden; and Boston, Mass. From the Department of General Surgery, University of Kentucky; Department of General Surgery, Johns Hopkins University; Department of Plastic Surgery, Padova University; Department of Plastic Surgery, Changzheng Hospital; Department of Surgery, Mito Chuo Hospital; Department of General Surgery, Inova Fairfax Hospital; Department of Anatomy, Physiology, and Biochemistry, Swedish University of Agricultural Sciences; and Division of Plastic Surgery, Brigham and Women's Hospital and Harvard Medical School.
authors.forename: Julien
authors.initials: J
authors.lastname: Succar
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Douaiher
authors.forename: Luca
authors.initials: L
authors.lastname: Lancerotto
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Ryushiro
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: George
authors.initials: G
authors.lastname: Younan
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Orgill
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D053818:Chymases / Q000172:deficiency / Q000502:physiology*; D008407:Mast Cells / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054843:Negative-Pressure Wound Therapy; D009779:Occlusive Dressings; D012697:Serine Endopeptidases / Q000172:deficiency / Q000502:physiology*; D012867:Skin / Q000201:enzymology / Q000293:injuries*; D012879:Skin Physiological Phenomena; D053802:Tryptases / Q000172:deficiency / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*
chemical_list: D015415:Biomarkers; C509190:Tpsb2 protein, mouse; C509227:Cma1 protein, mouse; D012697:Serine Endopeptidases; C066932:mast cell protease 4; D053818:Chymases; D053802:Tryptases