Chemokine receptor CX3CR1 mediates skin wound healing by promoting macrophage and fibroblast accumulation and function
Chemokine receptor CX3CR1 mediates skin wound healing by promoting macrophage and fibroblast accumulation and function
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DOI：
10.4049/jimmunol.180.1.569
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发表时间：
2008-01-01
影响因子：
4.4
通讯作者：
Murphy, Philip M.
中科院分区：
文献类型：
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作者：
Ishida, Yuko;Gao, Ji-Liang;Murphy, Philip M.
伤口通过高度调节的自限性炎症反应愈合，然而，精确的炎症介质尚未完全描述。在这项研究中，我们报告说，在切除皮肤伤口愈合的小鼠模型中，趋化因子CX 3CL 1及其受体CX 3CR 1都高度诱导伤口部位; CX 3CL 1与巨噬细胞和内皮细胞共定位，而CX 3CR 1主要与巨噬细胞和成纤维细胞共定位。CX 3CR 1功能丧失延迟了CX 3CR 1敲除（KO）小鼠和输注抗CX 3CR 1中和抗体的野生型小鼠的伤口闭合。相反，从供体野生型小鼠而不是供体CX 3CR 1 KO小鼠转移骨髓，使CX 3CR 1 KO受体小鼠的伤口愈合恢复正常。CX 3CR 1破坏在伤口部位的直接影响包括巨噬细胞和巨噬细胞产物的显著减少，如TGF-β 1和血管内皮生长因子。与此一致，我们观察到受伤的CX 3CR 1 KO小鼠皮肤中的α-平滑肌肌动蛋白（肌成纤维细胞的标志物）和胶原沉积减少，以及新血管形成减少。总之，这些数据支持皮肤伤口修复的分子模型，其中CX 3CR 1介导骨髓来源的单核细胞/巨噬细胞的直接募集，这些单核细胞/巨噬细胞释放促纤维化和血管生成介质。
Wounds heal through a highly regulated, self-limited inflammatory response, however, precise inflammatory mediators have not been fully delineated. In this study, we report that in a mouse model of excisional skin wound healing the chemokine CX3CL1 and its receptor CX3CR1 were both highly induced at wound sites; CX3CL1 colocalized with macrophages and endothelial cells, whereas CX3CR1 colocalized mainly with macrophages and fibroblasts. Loss of CX3CR1 function delayed wound closure in both CX3CR1 knockout (KO) mice and in wild-type mice infused with anti-CX3CR1-neutralizing Ab. Conversely, transfer of bone marrow from donor wild-type mice, but not from donor CX3CR1 KO mice, restored wound healing to normal in CX3CR1 KO-recipient mice. Direct effects of CX3CR1 disruption at the wound site included marked reduction of macrophages and macrophage products, such as TGF-beta 1 and vascular endothelial growth factor. Consistent with this, we observed reduced a-smooth muscle actin (a marker for myofibroblasts) and collagen deposition in skin from wounded CX3CR1 KO mice, as well as reduced neovascularization. Together, the data support a molecular model of skin wound repair in which CX3CR1 mediates direct recruitment of bone marrow-derived monocytes/macrophages which release profibrotic and angiogenic mediators.