Mast cells are required for normal healing of skin wounds in mice
Mast cells are required for normal healing of skin wounds in mice
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DOI：
10.1096/fj.06-5837fje
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发表时间：
2006-11-01
期刊：
影响因子：
4.8
通讯作者：
Maurer, Marcus
中科院分区：
文献类型：
--
作者：
Weller, Karsten;Foitzik, Kerstin;Maurer, Marcus
肥大细胞（MC）最近被报道在引发对宿主有益的炎症反应中起关键作用，例如，肥大细胞（MC）是一种重要的细胞因子。例如，在一个实施例中，对细菌的先天免疫反应。为了探索MC是否也有助于伤口修复，我们研究了MC缺陷Kit（W）/Kit（W-v）小鼠、正常Kit+/+小鼠和MC重建Kit（W）/Kit（W-v）小鼠中实验诱导的皮肤伤口。在伤口愈合的前6天，在没有MC的情况下，伤口闭合显著受损，并且伤口边缘处MC脱粒的组织形态学分析揭示了距离依赖性MC活化，即，MC脱颗粒最突出的直接邻近伤口。此外，Kit（W）/Kit（W-v）小鼠显示出渗出受损和中性粒细胞向受伤区域的募集。值得注意的是，在MC-重建的Kit（W）/Kit（W-v）小鼠中发现伤口闭合、外渗和中性粒细胞募集是正常的。因此，我们研究了MC是否通过释放组胺或TNF-α促进伤口愈合。有趣的是，在用H-1受体拮抗剂治疗的小鼠中，伤口闭合减少，但在用H-2受体拮抗剂治疗后或在没有TNF-α的情况下，伤口闭合没有减少。两者合计，我们的研究结果表明，MC激活和组胺释放所需的正常皮肤伤口愈合。
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-alpha. Interestingly, wound closure was reduced in mice treated with an H-1-receptor antagonist but not after treatment with an H-2-receptor antagonist or in the absence of TNF-alpha. Taken together, our findings indicate that MC activation and histamine release are required for normal cutaneous wound healing.