Effects of delayed delivery of dexamethasone-21-phosphate via subcutaneous microdialysis implants on macrophage activation in rats.
Effects of delayed delivery of dexamethasone-21-phosphate via subcutaneous microdialysis implants on macrophage activation in rats.
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DOI：
10.1016/j.actbio.2015.05.011
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发表时间：
2015-09
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
巨噬细胞活化在生物材料领域中是令人感兴趣的，因为具有M（Dex）特征表型的巨噬细胞，即，CD 68 + CD 163+被认为导致生物材料的改善的整合以及改善的组织重塑和增加的生物材料寿命。为了促进巨噬细胞调节剂地塞米松-21-磷酸（Dex）的递送，将微透析探针皮下植入雄性Sprague-Dawley大鼠中。Dex局部递送延迟至植入后第三天，作为改变植入部位巨噬细胞活化状态的手段。为了更好地阐明与M（Dex）巨噬细胞活化相关的分子机制，对透析液中的CCL 2进行定量，从植入物周围的切除组织中确定基因表达率，进行组织学分析和免疫组织化学分析（CD 68，CD 163）。Dex延迟输注导致与微透析探针接触的组织中转录水平的IL-6上调，并降低透析液中收集的CCL 2浓度。组织学分析显示，与对照组相比，Dex延迟输注后细胞密度增加。与作为对照的探针相比，Dex延迟输注导致微透析探针周围组织中CD 68 + CD 163+，M（Dex），巨噬细胞的百分比增加。
Macrophage activation is of interest in the biomaterials field since macrophages with an M(Dex) characteristic phenotype, i.e., CD68+CD163+, are believed to result in improved integration of the biomaterial as well as improved tissue remodeling and increased biomaterial longevity. To facilitate delivery of a macrophage modulator, dexamethasone-21-phosphate (Dex), microdialysis probes were subcutaneously implanted in male Sprague-Dawley rats. Dex localized delivery was delayed to the third day post implantation as means to alter macrophage activation state at an implant site. To better elucidate the molecular mechanisms associated with M(Dex) macrophage activation, CCL2 was quantified in dialysates, gene expression ratios were determined from excised tissue surrounding the implant, histological analyses, and immunohistochemical analyses (CD68, CD163) were performed. Dex delayed infusion resulted in the up-regulation of IL-6 at the transcript level in the tissue in contact with the microdialysis probe and decreased CCL2 concentrations collected in dialysates. Histological analyses showed increased cellular density as compared to controls in response to Dex delayed infusion. Dex delayed infusion resulted in an increased percentage of CD68+CD163+, M(Dex), macrophages in the tissue surrounding the microdialysis probe as compared to probes that served as controls.