ANTIBODY REACTIVITY TO PHOSPHORYLCHOLINE

项目5：人类抗体对磷胆碱的反应性：par依赖性生物活性的调节，含磷胆碱菌斑细菌的诱导，以及与牙周破坏的关系。抗体对磷胆碱（PC）的反应已被广泛研究，但其在人类中的生物学意义尚不清楚。据认为，大多数人抗pc反应反映了以前暴露于肺炎链球菌，但这种反应对肺炎链球菌感染的保护性质是值得怀疑的。我们发现牙周附着丧失患者的抗pc水平明显高于健康受试者。此外，我们的初步数据和其他研究小组的最新数据表明，许多牙菌斑细菌种类，包括一些链球菌、放线菌、有核梭菌、嗜蚜梭菌和放线菌属，都携带含有pc的抗原。我们的初步研究还表明，人抗pc可与脂质介质血小板活化因子（PAF）发生反应。在研究中，我们试图了解PC深刻抑制IgG2产生的机制，就像PAF受体拮抗剂一样。这些发现和我们的基本假设的含义是，抗pc抗体可能是由牙周附着丧失和炎症患者的口腔微生物诱导的，这些抗体可能影响PAF依赖性的生物活性。我们建议研究人类抗pc对这些功能的影响，包括IgG2的产生、细胞因子的释放和PMN的转运。同样令人感兴趣的是，肺炎链球菌通过利用其PC抗原模拟PAF分子并进入内皮细胞并进行迁移来进入循环。我们的初步数据表明，口腔抗原模仿PAF分子进入内皮细胞并迁移。我们的初步数据表明，口腔细菌如血链球菌、放线菌、放线菌comitans和F. nucleatum也可能利用这一途径。这也许可以解释牙周炎患者体内抗pc水平高的原因。此外，通过这种途径进入血液循环的能力可能在增加心内膜炎和心血管疾病的风险方面很重要。因此，我们建议进一步研究人体抗PC反应的生物学意义以及口腔细菌利用PC进入循环的可能性。

Project 5: Human antibody reactivity to phosphorylcholine: modulation of PAR-dependent biological activities, induction by phosphoryl choline- bearing plaque bacteria, and relationship to periodontal destruction. The antibody response to phosphorylcholine (PC) has been extensively studied, yet its biological significance in humans is poorly understood. It is thought that the majority of human anti-PC reflects previous exposure to S. pneumoniae, but the protective nature of this response against infection with S. pneumoniae is questionable. We have found that human anti-PC levels are significantly higher in patients who have experienced periodontal attachment loss than in healthy subjects. Furthermore, our preliminary data and recent data from other groups indicate that a number of dental plaque bacteria species, including several streptococci, actinomycetes, and strains of F. nucleatum, H. aphrophilus, and A. actinomycetemcomitans bear PC-containing antigens. Our preliminary studies also show that human anti-PC reacts with the lipid mediator platelet-activating factor (PAF). In studies in which we have sought to understand the mechanisms PC profoundly inhibits IgG2 production, as does a PAF receptor antagonist. The implication of these findings, and our fundamental hypothesis, is that anti-PC antibodies may be induced in humans by oral microorganisms in patients with periodontal attachment loss and inflammation, and that these antibodies could impact on PAF- dependent biological activities. We propose to examine the effects of human anti-PC on such functions, including IgG2 production, cytokine release, and PMN transmigration. It is also of interest that S. pneumoniae accesses the circulation by utilizing its PC antigen to mimic the PAF molecule and enter and transmigrate endothelial cells. Our preliminary data indicate that oral antigen to mimic the PAF molecule and enter and transmigrate endothelial cells. Our preliminary data indicate that oral bacteria such as S. sanguis, actinomycetes, A. actinomycetemcomitans, and F. nucleatum may also utilize this pathway. This may explain the high levels of anti-PC in periodontitis patients. Furthermore, the ability to access the circulation by this pathway could be important in promoting risk for endocarditis and cardiovascular disease. We therefore propose to further study the biological significance of the human anti-PC response as well as the possibility that oral bacterial utilize PC to enter the circulation.