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[用亲脂性糖缀合物修饰靶细胞表面以及修饰细胞与自然杀伤细胞的相互作用]

[Modification of the target cell surface with lipophilic glycoconjugates and interaction of the modified cells with natural killer cells].

作者信息

Kovalenko E I, Khirova E V, Molotkovskaia I M, Ovchinnikova T V, Sablina M A, Sapozhnikov A M, Khaĭdukov S V, Bovin N V

出版信息

Bioorg Khim. 2004 May-Jun;30(3):281-92. doi: 10.1023/b:rubi.0000030132.51210.16.

Abstract

An experimental model system involving the modification of carbohydrate composition of the target cell surface with neoglycolipids was developed for studying the role of surface carbohydrates of target cells in the NK-cell-mediated cytotoxicity. The polymeric glycoconjugates of the Glyc-PAA-PEA and Glyc-PAA(Flu)-PEA types (where Glyc was an oligosaccharide residue, PAA poly(acrylamide) polymer, and PEA the phosphatidylethanolamine residue, and Flu fluorescein residue) capable of incorporation into the cell membrane were synthesized. The optimum structures of neoglycoconjugates and conditions for their incorporation into K562 and Raji cell lines, which differ in their sensitivity to the NK-cell-mediated lysis were selected. The mechanism of association of glycoconjugates with the plasma cell membrane and the kinetics of their elimination from the cell surface were investigated using the fluorescent-labeled Glyc-PAA(Flu)-PEA derivatives. The spatial accessibility of the carbohydrate ligands for the interaction with human NK cells was demonstrated. The target cells modified with the Le(x) trisaccharide were shown to be more sensitive to the cytotoxic effect of human NK cells than the intact cells. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 3; see also http://www.maik.ru.

摘要

为研究靶细胞表面碳水化合物在自然杀伤细胞(NK 细胞)介导的细胞毒性中的作用,开发了一种实验模型系统,该系统涉及用新糖脂修饰靶细胞表面的碳水化合物组成。合成了能够掺入细胞膜的 Glyc-PAA-PEA 和 Glyc-PAA(Flu)-PEA 类型的聚合糖缀合物(其中 Glyc 是寡糖残基,PAA 是聚(丙烯酰胺)聚合物,PEA 是磷脂酰乙醇胺残基,Flu 是荧光素残基)。选择了新糖缀合物的最佳结构及其掺入对 NK 细胞介导的裂解敏感性不同的 K562 和 Raji 细胞系的条件。使用荧光标记的 Glyc-PAA(Flu)-PEA 衍生物研究了糖缀合物与质膜结合的机制及其从细胞表面消除的动力学。证明了碳水化合物配体与人类 NK 细胞相互作用的空间可及性。结果表明,用 Le(x)三糖修饰的靶细胞比完整细胞对人类 NK 细胞的细胞毒性作用更敏感。该论文的英文版:《俄罗斯生物有机化学杂志》,2004 年,第 30 卷,第 3 期;另见 http://www.maik.ru。

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