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揭开岩藻糖基化的神秘面纱:从细胞黏附到免疫系统调节与疾病。

Unmasking Fucosylation: from Cell Adhesion to Immune System Regulation and Diseases.

机构信息

Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Birmingham VA Medical Center, Birmingham, AL 35294, USA.

出版信息

Cell Chem Biol. 2018 May 17;25(5):499-512. doi: 10.1016/j.chembiol.2018.02.005. Epub 2018 Mar 8.

Abstract

Fucosylation is a biological process broadly observed in vertebrates, invertebrates, plants, bacteria, and fungi. Fucose moieties on cell-surface glycans are increasingly recognized as critical to many cell-cell interaction and signaling processes. One of the characteristic roles of fucose is its regulation of selectin-dependent leukocyte adhesion that has been well studied over the last two decades. Recent studies of fucose in immune cell development and function regulation have significantly expanded the contemporary understanding of fucosylation. From cellular adhesion to immune regulation, herein we discuss the use of gene knockout studies, competitive inhibitors of fucose-containing glycan, and metabolic inhibitors of fucose biosynthesis to probe fucosylated glycan biosynthesis and signaling and its functional consequences. Promising clinical and preclinical applications in sickle cell disease, rheumatoid arthritis, tumor inhibition, metastasis prevention, antibody-dependent cell-mediated cytotoxicity, chemoresistance reversal, and in improving chemotherapy-related side effects and recovery are reviewed.

摘要

岩藻糖基化是一种广泛存在于脊椎动物、无脊椎动物、植物、细菌和真菌中的生物过程。细胞表面糖链上的岩藻糖基已被越来越多地认识到对许多细胞-细胞相互作用和信号转导过程至关重要。岩藻糖的一个特征作用是调节选择素依赖性白细胞黏附,这在过去二十年中得到了很好的研究。近年来对免疫细胞发育和功能调节中的岩藻糖的研究极大地扩展了对岩藻糖基化的当代理解。从细胞黏附到免疫调节,本文讨论了使用基因敲除研究、岩藻糖含量聚糖的竞争抑制剂和岩藻糖生物合成的代谢抑制剂来探测岩藻糖基化聚糖的生物合成和信号转导及其功能后果。在镰状细胞病、类风湿关节炎、肿瘤抑制、转移预防、抗体依赖性细胞介导的细胞毒性、化疗耐药逆转以及改善化疗相关副作用和恢复方面的有前途的临床前和临床应用得到了综述。

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