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树突状细胞样细胞的聚糖结合谱。

Glycan-binding profile of DC-like cells.

机构信息

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, 16/10, Miklukho-Maklaya str., Moscow, 117997, Russia.

Institute of Virology and Immunology, Sensemattstrasse 293, CH-3147, Mittelhäusern, Switzerland.

出版信息

Glycoconj J. 2020 Feb;37(1):129-138. doi: 10.1007/s10719-019-09897-9. Epub 2019 Dec 13.

Abstract

Modification of vaccine carriers by decoration with glycans can enhance binding to and even targeting of dendritic cells (DCs), thus augmenting vaccine efficacy. To find a specific glycan-"vector" it is necessary to know glycan-binding profile of DCs. This task is not trivial; the small number of circulating blood DCs available for isolation hinders screening and therefore advancement of the profiling. It would be more convenient to employ long-term cell cultures or even primary DCs from murine blood. We therefore examined whether THP-1 (human monocyte cell line) and DC2.4 (immature murine DC-like cell line) could serve as a model for human DCs. These cells were probed with a set of glycans previously identified as binding to circulating human CD14CD16CD83 DCs. In addition, we tested a subpopulation of murine CD14CD80СD11cCD16 cells reported as relating to the human CD14CD16CD83 cells. Manα1-3(Manα1-6)Manβ1-4GlcNAcβ1-4GlcNAcβ bound to both the cell lines and the murine CD14CD80СD11cCD16 cells. Primary cells, but not the cell cultures, were capable of binding GalNAcα1-3Galβ (A), the most potent ligand for binding to human circulating DCs. In conclusion, not one of the studied cell lines proved an adequate model for DCs processes involving lectin binding. Although the glycan-binding profile of BYRB-Rb (8.17)1Iem mouse DCs could prove useful for assessing human DCs, important glycan interactions were missing, a situation which was aggravated when employing cells from the BALB/c strain. Accordingly, one must treat results from murine work with caution when seeking vaccine targeting of human DCs, and certainly should avoid cell lines such as THP-1 and DC2.4 cells.

摘要

通过糖基化修饰疫苗载体可以增强与树突状细胞(DCs)的结合,甚至可以靶向 DCs,从而提高疫苗的疗效。为了找到特定的糖基-“载体”,有必要了解 DCs 的糖基结合谱。这项任务并不简单;可用于分离的循环血液 DC 数量较少,这阻碍了筛选,从而也阻碍了对其特征的进一步研究。使用长期细胞培养物甚至来自鼠血液的原代 DC 会更方便。因此,我们研究了 THP-1(人单核细胞系)和 DC2.4(不成熟的鼠类树突状细胞样细胞系)是否可以作为人 DC 的模型。我们用一组先前鉴定为与人循环 CD14CD16CD83 DC 结合的糖基来探测这些细胞。此外,我们还测试了一种被报道与人 CD14CD16CD83 细胞相关的鼠 CD14CD80CD11cCD16 细胞亚群。Manα1-3(Manα1-6)Manβ1-4GlcNAcβ1-4GlcNAcβ 结合到这两种细胞系和鼠 CD14CD80CD11cCD16 细胞上。只有原代细胞而不是细胞培养物能够结合 GalNAcα1-3Galβ(A),这是与循环人 DC 结合的最有效配体。总之,在所研究的细胞系中,没有一个被证明是涉及凝集素结合的 DC 过程的合适模型。尽管 BYRB-Rb(8.17)1Iem 鼠 DC 的糖基结合谱可能有助于评估人 DC,但重要的糖基相互作用缺失了,当使用来自 BALB/c 品系的细胞时,这种情况更加严重。因此,在寻找针对人 DC 的疫苗靶向时,必须谨慎对待来自鼠类的研究结果,当然,应避免使用 THP-1 和 DC2.4 细胞等细胞系。

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