SIALYL LEWIS X IN RISK ASSESSMENT FOR PERIODONTAL DISEASE

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。虽然微生物粘附和/或从口腔中清除是许多因素复杂相互作用的结果，但细菌蛋白质（例如，粘附素、凝集素）和唾液分子的碳水化合物部分通常是该过程的重要组分。费舍尔实验室在过去十年中完成的结构工作导致了一个意想不到的发现，即单个唾液糖蛋白携带独特的寡糖结构。此外，我们证明了这些糖蛋白特异性的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一个重要因素。最近，我们发现，我们的67个唾液捐赠者的5个唾液样本缺乏促进白细胞粘附的表位，唾液酸Lex（sLex），但仍然表达作为细菌受体的寡糖。缺乏编码sLex的糖基转移酶的小鼠和人类的免疫功能大大受损。在这种情况下，我们提出，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一种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。

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.