The Role of Mouse Mast Cell Proteases in the Proliferative Phase of Wound Healing in Microdeformational Wound Therapy

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 microdefoimational wound therapy was disrupted.Conclusion: Results suggest that mouse mast cell proteases 4, 5, and 6 are mediators of the critical role mast cells play in microdefoi national wound therapy in the proliferative phase of healing.