Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response.
Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response.
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DOI：
10.1016/j.jconrel.2015.09.021
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发表时间：
2015-11-10
期刊：
影响因子：
--
通讯作者：
Perretti M
中科院分区：
文献类型：
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作者：
Federici Canova D;Pavlov AM;Norling LV;Gobbetti T;Brunelleschi S;Le Fauder P;Cenac N;Sukhorukov GB;Perretti M
合成的微结构可以被工程化以递送影响其药代动力学和药效学的生物活性化合物。本文中，我们应用基于葡聚糖的逐层（LbL）微胶囊来递送α-2-巨球蛋白（α 2 MG），α 2 MG是一种在炎症中具有调节特性的蛋白质。扩展了最近在实验性脓毒症中使用载有α 2 MG的葡聚糖微胶囊进行的观察，我们专注于这些微结构的物理和化学特征，并确定了它们在啮齿动物和人类细胞上的生物学特性。我们报告了α 2 MG有效包封到微胶囊中，其增强i）人白细胞募集到发炎的内皮和ii）人巨噬细胞吞噬作用：在两种情况下，微胶囊比可溶性α 2 MG或空微胶囊（缺乏活性蛋白）更有效。这些结果的转化表明，静脉给予α 2 MG-微胶囊（而非空微胶囊）可促进中性粒细胞迁移至腹膜渗出液中，并增强巨噬细胞吞噬功能，后者的反应与质谱法评估的生物活性脂质介质的改变相关。目前的研究表明，微囊化可以成为利用α 2 MG复杂生物学的有效策略，增强先天免疫应答基本过程的结果，为脓毒症控制的潜在未来发展铺平道路。
Synthetic microstructures can be engineered to deliver bioactive compounds impacting on their pharmacokinetics and pharmacodynamics. Herein, we applied dextran-based layer-by-layer (LbL) microcapsules to deliver alpha-2-macroglobulin (α2MG), a protein with modulatory properties in inflammation. Extending recent observations made with dextran-microcapsules loaded with α2MG in experimental sepsis, we focused on the physical and chemical characteristics of these microstructures and determined their biology on rodent and human cells. We report an efficient encapsulation of α2MG into microcapsules, which enhanced i) human leukocyte recruitment to inflamed endothelium and ii) human macrophage phagocytosis: in both settings microcapsules were more effective than soluble α2MG or empty microcapsules (devoid of active protein). Translation of these findings revealed that intravenous administration of α2MG-microcapsules (but not empty microcapsules) promoted neutrophil migration into peritoneal exudates and augmented macrophage phagocytic functions, the latter response being associated with alteration of bioactive lipid mediators as assessed by mass spectrometry. The present study indicates that microencapsulation can be an effective strategy to harness the complex biology of α2MG with enhancing outcomes on fundamental processes of the innate immune response paving the way to potential future development in the control of sepsis.