The preservation of phenotype and functionality of dendritic cells upon phagocytosis of polyelectrolyte-coated PLGA microparticles
The preservation of phenotype and functionality of dendritic cells upon phagocytosis of polyelectrolyte-coated PLGA microparticles
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DOI：
10.1016/j.biomaterials.2006.10.034
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发表时间：
2007-02-01
期刊：
影响因子：
14
通讯作者：
Gander, Bruno
中科院分区：
文献类型：
--
作者：
Fischer, Stefan;Uetz-von Allmen, Edith;Gander, Bruno
生物可降解微粒（MP）代表了一种有前途的和有效的胃肠外疫苗接种系统。最近，MP也已被探索作为离体抗原负载的专职抗原呈递细胞如树突状细胞（DC）的工具，以用作细胞疫苗。本研究的目的是研究聚（丙交酯-共-乙交酯）（PLGA）MP上的各种聚阳离子涂层，关于它们对先前在体外加载MP的单核细胞来源的DC（MoDC）的表型和功能成熟的影响。PLGA的制备和伴随的涂层通过溶剂萃取/蒸发方法使用最近开发的基于微挤出的技术进行。用于MP涂层测试的聚电解质包括氨基葡聚糖、壳聚糖、聚（乙烯亚胺）（PEI）、聚（L-赖氨酸）和鱼精蛋白。将未涂覆的和不同涂覆的PLGA MP进料至未成熟的MoDC，其有效地摄取不同的MP类型，而不管其表面涂覆。然后在细胞因子/PGE-2成熟混合物的帮助下使MP负载的未成熟MoDC成熟。在此，摄入的MP的存在不影响MoDC在表面标志物CD 80、CD 83、CD 86、HLA-DR和MMR的表达方面的成熟，而与MP表面包被无关。重要的是，在不存在成熟混合物的情况下，单独的PLGA MP类型均不诱导MoDC的显著成熟。MP加载和随后成熟的MoDC表达高水平的趋化因子受体CCR 7，其功能活性被证明是由MoDC向CCL 21的迁移，无论是否存在摄入的MP。此外，除了PEI包被的PLGA MP外，MP负载的随后成熟的MoDC也分泌相当量的IL-10和IL-12 p70，而不管是否存在摄入的MP，其显著增强成熟MoDC中IL-12 p70的分泌。总之，通过成熟混合物的MoDC的表型和功能成熟保持不变，而不管先前摄入的不同涂层的PLGA MP的存在。这提供了有趣的观点，使用这些颗粒系统与包埋的抗原一起用于MoDC的离体负载，鉴于细胞免疫治疗。(c)2006爱思唯尔有限公司保留所有权利。
Biodegradable microparticles (MP) represent a promising and efficient delivery system for parenteral vaccination. Recently, MP have also been explored as tool for the ex vivo antigen loading of professional antigen-presenting cells such as dendritic cells (DC) to be used as cellular vaccines. The purpose of this study was to investigate various polycationic coatings on poly(lactide-co-glycolide) (PLGA) MP, with regard to their effect on phenotypic and functional maturation of monocyte-derived DC (MoDC) that had previously been loaded with the MP in vitro. The preparation and concomitant coating of the PLGA was performed by means of a solvent extraction/ evaporation method using a recently developed microextrusion-based technique. The polyelectrolytes tested for MP coating encompassed aminodextran, chitosan, poly(ethylene imine) (PEI), poly(L-lysine) and protamine. Uncoated and differently coated PLGA MP were fed to immature MoDC, which ingested efficiently the different MP types irrespective of their surface coating. The MP-loaded immature MoDC were then matured with the help of a cytokine/PGE-2 maturation cocktail. Here, the presence of the ingested MP did not affect the MoDC maturation in terms of expression of the surface markers CD80, CD83, CD86, HLA-DR and MMR, irrespective of the MP surface coating. Importantly, none of the PLGA MP types alone induced significant maturation of MoDC in the absence of the maturation cocktail. MP-loaded and subsequently matured MoDC expressed high levels of the chemokine receptor CCR7, whose functional activity was evidenced by the migration of MoDC towards CCL21, irrespective of the presence of ingested MP. Further, MP-loaded and subsequently matured MoDC also secreted comparable amounts of IL-10 and IL-12p70, irrespective of the presence of ingested MP except for PEI-coated PLGA MP, which enhanced significantly the secretion of IL-12p70 in mature MoDC. In conclusion, phenotypic and functional maturation of MoDC by means of a maturation cocktail remained unchanged irrespective of the presence of previously ingested differently coated PLGA MP. This offers interesting perspectives for using these particulate systems together with entrapped antigens for ex vivo loading of MoDC in view of cellular immunotherapy. (c) 2006 Elsevier Ltd. All rights reserved.