Cell plasticity in wound healing: paracrine factors of M1/ M2 polarized macrophages influence the phenotypical state of dermal fibroblasts.
Cell plasticity in wound healing: paracrine factors of M1/ M2 polarized macrophages influence the phenotypical state of dermal fibroblasts.
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DOI：
10.1186/1478-811x-11-29
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发表时间：
2013-04-19
期刊：
影响因子：
--
通讯作者：
Bank RA
中科院分区：
文献类型：
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作者：
Ploeger DT;Hosper NA;Schipper M;Koerts JA;de Rond S;Bank RA
巨噬细胞和成纤维细胞是组织修复和纤维化的两个主要参与者。尽管巨噬细胞和成纤维细胞在组织内稳态中的相关性，但巨噬细胞是否能够影响成纤维细胞的性质知之甚少。在这里，我们研究了旁分泌因子分泌的经典激活（M1）和交替激活（M2）人巨噬细胞对人皮肤成纤维细胞（HDF）的作用。用来自M1巨噬细胞的旁分泌因子刺激的HDF显示炎性细胞因子IL 6、CCL 2和CCL 7以及基质金属蛋白酶MMP 1和MMP 3的表达增加10至> 100倍。这表明M1巨噬细胞产生的因子诱导具有促炎和细胞外基质（ECM）降解特性的成纤维细胞表型。由M2巨噬细胞分泌的旁分泌因子刺激的HDFs显示出增加的增殖率。有趣的是，在暴露于由M2巨噬细胞或非条件培养基产生的旁分泌因子后，M1活化的促炎成纤维细胞下调炎症标记物以及MMPs，并上调其胶原蛋白的产生。M1或M2极化的巨噬细胞的旁分泌因子诱导了HDF的不同表型，HDF表型可以反过来逆转，这表明成纤维细胞在组织修复的不同阶段具有高的动态可塑性。
Macrophages and fibroblasts are two major players in tissue repair and fibrosis. Despite the relevance of macrophages and fibroblasts in tissue homeostasis, remarkably little is known whether macrophages are able to influence the properties of fibroblasts. Here we investigated the role of paracrine factors secreted by classically activated (M1) and alternatively activated (M2) human macrophages on human dermal fibroblasts (HDFs). HDFs stimulated with paracrine factors from M1 macrophages showed a 10 to > 100-fold increase in the expression of the inflammatory cytokines IL6, CCL2 and CCL7 and the matrix metalloproteinases MMP1 and MMP3. This indicates that factors produced by M1 macrophages induce a fibroblast phenotype with pro-inflammatory and extracellular matrix (ECM) degrading properties. HDFs stimulated with paracrine factors secreted by M2 macrophages displayed an increased proliferation rate. Interestingly, the M1-activated pro-inflammatory fibroblasts downregulated, after exposure to paracrine factors produced by M2 macrophages or non-conditioned media, the inflammatory markers as well as MMPs and upregulated their collagen production. Paracrine factors of M1 or M2 polarized macrophages induced different phenotypes of HDFs and the HDF phenotypes can in turn be reversed, pointing to a high dynamic plasticity of fibroblasts in the different phases of tissue repair.