Highly glycosylated human salivary molecules present oligosaccharides that mediate adhesion of leukocytes and Helicobacter pylori.
Highly glycosylated human salivary molecules present oligosaccharides that mediate adhesion of leukocytes and Helicobacter pylori.
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高度糖基化的人类唾液分子呈现寡糖，介导白细胞和幽门螺杆菌的粘附。
DOI：
10.1021/bi0480180
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Fisher,SusanJ
中科院分区：
文献类型：
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作者：
Prakobphol,Akraporn;Boren,Thomas;Ma,Wenge;Zhixiang,Peng;Fisher,SusanJ
糖蛋白显示碳水化合物面，作为细胞的粘附受体，包括白细胞和细菌细胞。我们的目的是了解由高度糖基化的人类唾液蛋白携带的特殊碳水化合物基序在调节口腔生态中的作用。迄今为止，我们的结构研究表明，这些分子显示出广泛的低聚糖结构，包括许多具有高电荷和/或聚焦末端的物种。在这里，我们使用免疫印迹方法来获得关于这些低聚糖性质的额外信息。结果表明，MG1和唾液凝集素表达MECA-79表位，这是一种罕见的硫酸化碳水化合物结构，属于一类重要的高亲和力（内皮）l -选择素配体。出乎意料的是，我们发现在许多女性中这种表位的表达是受激素调节的。另外的实验显示，MG1、MG2和唾液凝集素也呈现Lewis血型抗原，具体的抗原种类因个体而异。同时，我们探索了这些碳水化合物基序的功能。利用检测l -选择素配体的实验，我们发现唾液分子上显示的meca -79反应性低聚糖亚群特异性地结合l -选择素/Fc嵌合体。相反，Lewis血型结构是许多幽门螺杆菌菌株的受体，幽门螺杆菌是一种与胃溃疡和癌症的发展有关的有机体。总之，这些结果表明MG1、MG2和唾液凝集素在控制白细胞和细菌粘附中起重要作用。我们的发现提出了新的策略，基于相关的碳水化合物结构，促进或抑制这些过程。
Glycoproteins display carbohydrate facets that serve as adhesion receptors for cells including leukocytes and bacterial cells. Our aim was to understand the role of the specialized carbohydrate motifs carried by highly glycosylated human salivary proteins in regulating the oral ecology. To date, our structural studies suggest that these molecules display a wide array of oligosaccharide structures, including many species with highly charged and/or fucosylated termini. Here, we used an immunoblot approach to gain additional information about the nature of these oligosaccharides. The results showed that MG1 and the salivary agglutinin express the MECA-79 epitope, an unusual sulfated carbohydrate structure that belongs to an important class of high-affinity (endothelial) L-selectin ligands. Unexpectedly, we discovered that in many women the expression of this epitope is hormonally regulated. Additional experiments revealed that MG1, MG2, and the salivary agglutinin also present Lewis blood group antigens, the exact repertoire varying on an individual basis. In parallel, we explored the functions of these carbohydrate motifs. Using an assay that detects L-selectin ligands, we found that the subset of MECA-79-reactive oligosaccharides displayed on salivary molecules specifically bind an L-selectin/Fc chimera. In contrast, the Lewis blood group structures are receptors for many strains ofHelicobacter pylori, an organism that is implicated in the development of gastric ulcers and cancer. Together, these results suggest that MG1, MG2, and the salivary agglutinin play important roles in governing leukocyte and bacterial adhesion. Our findings suggest novel strategies, based on the relevant carbohydrate structures, for promoting or inhibiting these processes.