Polyanhydride microparticles enhance dendritic cell antigen presentation and activation.
Polyanhydride microparticles enhance dendritic cell antigen presentation and activation.
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DOI：
10.1016/j.actbio.2011.03.023
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发表时间：
2011-07
影响因子：
9.7
通讯作者：
Narasimhan, Balaji
中科院分区：
文献类型：
--
作者：
Torres, Maria P.;Wilson-Welder, Jennifer H.;Lopac, Senja K.;Phanse, Yashdeep;Carrillo-Conde, Brenda;Ramer-Tait, Amanda E.;Bellaire, Bryan H.;Wannemuehler, Michael J.;Narasimhan, Balaji
本研究旨在评估在不存在额外的稳定剂、赋形剂或免疫调节剂的情况下制备的聚酸酐微粒的佐剂活性。将由不同比例的1，6-双（对羧基苯氧基）己烷（CPH）和癸二酸（SA）或1，8-双（对羧基苯氧基）-3，6-二氧杂辛烷（CPTEG）和CPH组成的微粒加入骨髓来源的树突状细胞（DC）的体外培养物中。在不存在调理作用且不离心或搅拌的情况下，微粒被DC有效且快速地吞噬。在2小时内，内化颗粒迅速定位于酸性，吞噬溶酶体室。到48 h时，在吞噬溶酶体隔室中仅观察到微粒尺寸轻微减小，表明与位于有利于颗粒稳定性的细胞内微环境内一致的最小颗粒侵蚀。聚酸酐微粒增加DC表面MHC II、共刺激分子CD 86和CD 40以及C型凝集素CIRE（鼠DC-SIGN; CD 209）的表达。此外，DC的微粒刺激也增强了细胞因子IL-12 p40和IL-6的分泌，发现这种现象依赖于聚合物化学。用聚酸酐微粒和卵白蛋白培养的DC诱导CD 4 + OT-II和CD 8 + OT-I T细胞的聚合物化学依赖性抗原特异性增殖。这些数据表明，聚酸酐颗粒可以被定制以利用免疫应答的潜在可塑性，从而能够诱导针对许多类型的病原体的免疫保护。
The present studies were designed to evaluate the adjuvant activity of polyanhydride microparticles prepared in the absence of additional stabilizers, excipients, or immune modulators. Microparticles composed of varying ratios of either 1,6-bis(p-carboxyphenoxy)hexane (CPH) and sebacic acid (SA) or 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and CPH were added to in vitro cultures of bone marrow-derived dendritic cells (DCs). Microparticles were efficiently and rapidly phagocytosed by DCs in the absence of opsonization and without centrifugation or agitation. Within 2 h, internalized particles were rapidly localized to an acidic, phagolysosomal compartment. By 48 h, only a minor reduction in microparticle size was observed in the phagolysosomal compartment, indicating minimal particle erosion consistent with being localized within an intracellular microenvironment favoring particle stability. Polyanhydride microparticles increased DC surface expression of MHC II, the co-stimulatory molecules CD86 and CD40, and the C-type lectin CIRE (murine DC-SIGN; CD209). In addition, microparticle stimulation of DCs also enhanced secretion of the cytokines IL-12p40 and IL-6, a phenomenon found to be dependent on polymer chemistry. DCs cultured with polyanhydride microparticles and ovalbumin induced polymer chemistry-dependent antigen-specific proliferation of both CD4+ OT-II and CD8+ OT-I T cells. These data indicate that polyanhydride particles can be tailored to take advantage of the potential plasticity of the immune response, resulting in the ability to induce immune protection against many types of pathogens.
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影响因子：
17.3
作者：
Cleland, JL
通讯作者：
Cleland, JL
影响因子：
14
作者：
Determan, AS;Wilson, JH;Narasimhan, B
通讯作者：
Narasimhan, B
影响因子：
14
作者：
Hanes, J;Chiba, M;Langer, R
通讯作者：
Langer, R
影响因子：
5.4
作者：
Barr, Tom A;Brown, Sheila;Ryan, Gemma;Zhao, Jiexin;Gray, David
通讯作者：
Gray, David
影响因子：
2.2
作者：
Lutz, MB;Kukutsch, N;Schuler, G
通讯作者：
Schuler, G