Presentation Modality of Glycoconjugates Modulates Dendritic Cell Phenotype.
Presentation Modality of Glycoconjugates Modulates Dendritic Cell Phenotype.
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DOI：
10.1039/c4bm00138a
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发表时间：
2014-10-01
影响因子：
6.6
通讯作者：
Babensee JE
中科院分区：
文献类型：
--
作者：
Hotaling NA;Ratner DM;Cummings RD;Babensee JE
比较树突状细胞（DC）对可溶性、可吞噬性或非可吞噬性糖缀合物的反应尚不清楚。这是特别成问题的，因为微阵列表面上存在的固定化聚糖的探测是基于聚糖的治疗剂的潜在候选物的常见筛选。然而，平坦表面上的碳水化合物-蛋白质相互作用可转化为有效疗法（例如以可溶性或可吞噬颗粒递送的疫苗）的开发的假设尚未得到验证。因此，进行了初步研究，其中甘露糖或葡萄糖缀合到阳离子化的牛血清白蛋白，并提交给DC的可溶性，吞噬，或非吞噬展示模式。通过高通量测定评估对糖缀合物的功能性DC应答。将树突状细胞表型结果置于多变量一般线性模型（GLM）中，并显示在比较相似表面积时显示模式之间存在统计学差异。GLM显示吸附到威尔斯孔的糖缀合物是最促炎的，而可溶性缀合物是最少的。发现DC与甘露糖缀合物的相互作用是钙依赖性的，并且可以通过抗DC-SIGN抗体抑制。本研究的结果旨在解决来自多个实验室的报告中的冲突，这些报告显示了对通过不同方式递送的类似（如果不相同）配体的不同DC曲线的响应。此外，本研究开始弥合微阵列结合数据和功能性细胞反应之间的差距，通过突出吸附的糖缀合物诱导的表型相比，在溶液中或微粒上显示。
The comparative dendritic cell (DC) response to glycoconjugates presented in soluble, phagocytosable, or non-phagocytosable display modalities is poorly understood. This is particularly problematic, as the probing of immobilized glycans presented on the surface of microarrays is a common screen for potential candidates for glycan-based therapeutics. However, the assumption that carbohydrate-protein interactions on a flat surface can be translatable to development of efficacious therapies, such as vaccines, which are delivered in soluble or phagocytosable particles, has not been validated. Thus, a preliminary investigation was performed in which mannose or glucose was conjugated to cationized bovine serum albumin and presented to DCs in soluble, phagocytosable, or non-phagocytosable display modalities. The functional DC response to the glycoconjugates was assessed via a high throughput assay. Dendritic cell phenotypic outcomes were placed into a multivariate, general linear model (GLM) and shown to be statistically different amongst display modalities when comparing similar surface areas. The GLM showed that glycoconjugates that were adsorbed to wells were the most pro-inflammatory while soluble conjugates were the least. DC interactions with mannose conjugates were found to be calcium dependent and could be inhibited via anti-DC-SIGN antibodies. The results of this study aim to resolve conflicts in reports from multiple laboratories showing differential DC profiles in response to similar, if not identical, ligands delivered via different modalities. Additionally, this study begins to bridge the gap between microarray binding data and functional cell responses by highlighting the phenotypes induced from adsorbed glycoconjugates as compared to those in solution or displayed on microparticles.