SIALYL LEWIS X IN RISK ASSESSMENT FOR PERIODONTAL DISEASE

SIALYL LEWIS X 参与牙周病风险评估

• 批准号: 6662804
• 负责人: SUSAN J. FISHER
• 金额: $ 3.06万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6662804
• 关键词: bacterial proteins; bactericidal immunity; biomarker; cell adhesion; cell adhesion molecules; clinical research; dental caries; genetic susceptibility; glycoproteins; human subject; oligosaccharides; periodontitis; phenotype; protein purification; saliva

One of the most interesting and biologically important functions of salivary glycoproteins is their ability to serve as bacterial receptors. Although microbial adhesion and/or clearance from the oral cavity is the result of a complex interplay of many factors, interactions between bacterial proteins (e.g., adhesin, lectins) and the carbohydrate portions of the salivary molecules are often an important component of the process. Structural work from the Fisher laboratory that was completed over the last decade resulted in the unexpected finding that individual salivary glycoproteins carry unique oligosaccharide structures. In addition, we demonstrated that these glycoprotein-specific carbohydrate sequences can direct either bacterial or neutrophil adherence to the molecules they modify. Together, these results suggest that the manner in which salivary proteins are glycosylated could be an important factor in determining oral health. Very recently we showed that saliva samples from 5 of our 67 saliva donors lack the epitope that promotes leukocyte adherence, sialyl Lex (sLex), but still express oligosaccharides that act as bacterial receptors. Mice and humans who lack the glycosyltransferase that encodes sLex have greatly impaired immune function. In this context, we propose that individuals with saliva that lacks the epitope have an increased risk of developing oral infections. As a first step toward testing this hypothesis, we will determine whether the sLex-phenotype is associated with the development of periodontitis and/or smooth surface caries. If this hypothesis proves correct, than our laboratory findings could lead to a test for predicting oral health, analogous to using IL-1 genotype as an indicator of susceptibility to severe periodontitis in adults.

唾液糖蛋白最有趣和生物学上最重要的功能之一是它们作为细菌受体的能力。尽管微生物在口腔中的粘附和/或清除是许多因素复杂相互作用的结果，但细菌蛋白（例如粘附素、凝集素）和唾液分子的碳水化合物部分之间的相互作用通常是该过程的重要组成部分。费舍尔实验室在过去十年中完成的结构工作得出了意想不到的发现，即单个唾液糖蛋白携带独特的寡糖结构。此外，我们证明这些糖蛋白特异性碳水化合物序列可以指导细菌或中性粒细胞粘附到它们修饰的分子上。总之，这些结果表明唾液蛋白糖基化的方式可能是决定口腔健康的重要因素。最近，我们发现 67 名唾液捐献者中有 5 名的唾液样本缺乏促进白细胞粘附的表位——唾液酸 Lex (sLex)，但仍表达充当细菌受体的寡糖。缺乏编码 sLex 的糖基转移酶的小鼠和人类的免疫功能严重受损。在这种情况下，我们建议唾液缺乏表位的个体发生口腔感染的风险增加。作为检验这一假设的第一步，我们将确定 sLex 表型是否与牙周炎和/或光滑表面龋齿的发展相关。如果这一假设被证明是正确的，那么我们的实验室研究结果可能会导致预测口腔健康的测试，类似于使用 IL-1 基因型作为成人严重牙周炎易感性的指标。