Localized delivery of dexamethasone-21-phosphate via microdialysis implants in rat induces M(GC) macrophage polarization and alters CCL2 concentrations.
Localized delivery of dexamethasone-21-phosphate via microdialysis implants in rat induces M(GC) macrophage polarization and alters CCL2 concentrations.
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DOI：
10.1016/j.actbio.2014.10.022
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发表时间：
2015-01
影响因子：
9.7
通讯作者：
Stenken JA
中科院分区：
文献类型：
--
作者：
Keeler GD;Durdik JM;Stenken JA
将微透析取样探针植入雄性 Sprague Dawley 大鼠背侧的皮下空间，局部递送 21-磷酸地塞米松 (Dex)，目的是改变体内巨噬细胞极化。巨噬细胞极化在生物材料领域具有重要意义，因为伤口愈合巨噬细胞是延长植入物寿命以及改善植入物组织重塑的可能手段。对收集的透析液中的 CCL2 进行定量分析，对微透析植入物周围的组织进行基因表达和免疫组织化学，用于评估 Dex 是否极化巨噬细胞。 Dex输注下调IL-6和CCL2基因表达，并降低植入部位收集的透析液中CCL2浓度。 Dex 似乎对 CD163（一种常用的 M2c 巨噬细胞表面标记）的基因调控没有显着影响；精氨酸2;和 iNOS2。然而，Dex 输注可有效增加植入的微透析探针周围 CD 163+ 细胞的数量。这项工作展示了使用微透析取样来递送 Dex 等试剂来改变体内巨噬细胞极化，同时能够收集周围微环境中的细胞因子。
Microdialysis sampling probes were implanted into the subcutaneous space on the dorsal side of male Sprague Dawley rats to locally deliver dexamethasone-21-phosphate (Dex) with the aim of altering in vivo macrophage polarization. Macrophage polarization is of significant interest in the field of biomaterials since wound healing macrophages are a possible means to extend implant life as well as improve tissue remodeling to an implant. Quantitative analysis of CCL2 in collected dialysates, gene expression and immunohistochemistry performed on the tissue surrounding the microdialysis implant were used to evaluate if Dex polarized macrophages. Dex infusion down regulated IL-6 and CCL2 gene expression and decreased CCL2 concentrations in dialysates collected at the implant site. Dex appeared to have no significant effect on the gene regulation of CD163, a commonly used M2c macrophage surface marker; Arg2; and iNOS2. However, Dex infusion was effective at increasing the number of CD 163+ cells surrounding the implanted microdialysis probe. This work demonstrates the use of microdialysis sampling to deliver agents such as Dex to alter macrophage polarization in vivo while allowing the ability to collect cytokines in the surrounding microenvironment.