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Mast cells are required for normal healing of skin wounds in mice

Karsten Weller^*,, Kerstin Foitzik, Ralf Paus, Wolfgang Syska^*,|| and Marcus Maurer^*,||,1

^* Department of Dermatology and Allergology, Allergie-Centrum-Charité, Charité – Universitätsmedizin Berlin, Berlin, Germany;

Department of Dermatology, University Hospital Würzburg, Würzburg, Germany;

Department of Dermatology, University Hospital Hamburg-Eppendorf, Hamburg, Germany;

Department of Dermatology, University Hospital Lübeck, Lübeck, Germany; and

^|| Department of Dermatology, University Hospital Mainz, Mainz, Germany

¹Correspondence: Department of Dermatology and Allergy, Charité – Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany. E-mail: marcus.maurer{at}charite.de

ABSTRACT

Mast cells (MCs) have recently been reported to play a pivotal role in the elicitation of inflammatory reactions that are beneficial to the host, e.g., during innate immune responses to bacteria. To explore whether MCs also contribute to wound repair, we studied experimentally induced skin wounds in MC-deficient Kit^W/Kit^W-v mice, normal Kit+/+ mice, and MC-reconstituted Kit^W/Kit^W-v mice. Wound closure was significantly impaired in the absence of MCs during the first 6 days of wound healing and histomorphometric analyses of MC degranulation at the wound edges revealed distance-dependent MC activation, i.e., MC degranulation was most prominent directly adjacent to the wound. In addition, Kit^W/Kit^W-v mice showed impaired extravasation and recruitment of neutrophils to the wounded areas. Notably, wound closure, extravasation, and neutrophil recruitment were found to be normal in MC-reconstituted Kit^W/Kit^W-v mice. Therefore, we examined whether MCs promote wound healing by releasing histamine or TNF-. Interestingly, wound closure was reduced in mice treated with an H₁-receptor antagonist but not after treatment with an H₂-receptor antagonist or in the absence of TNF-. Taken together, our findings indicate that MC activation and histamine release are required for normal cutaneous wound healing.—Weller, K., Foitzik, K., Paus, R., Syska, W., Maurer, M. Mast cells are required for normal healing of skin wounds in mice.

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