ANTIBODY REACTIVITY TO PHOSPHORYLCHOLINE

项目5：人类抗体对磷酰胆碱的反应性：依赖PAR的生物学活性的调节，携带磷酰胆碱的菌斑细菌的诱导，以及与牙周破坏的关系。对磷胆碱(PC)的抗体反应已被广泛研究，但对其在人类中的生物学意义知之甚少。大多数人的抗PC抗体被认为反映了以前接触过肺炎链球菌，但这种反应对肺炎链球菌感染的保护性是值得怀疑的。我们发现，在经历过牙周附着丧失的患者中，人类抗PC水平显著高于健康受试者。此外，我们的初步数据和来自其他小组的最新数据表明，一些牙菌斑细菌物种，包括几种链球菌、放线菌，以及核杆菌、嗜人嗜血杆菌和伴放线放线菌都携带含有PC的抗原。我们的初步研究还表明，人抗PC与脂质介质血小板激活因子(PAF)发生反应。在我们试图了解PC深刻抑制IgG2产生的机制的研究中，PAF受体拮抗剂也是如此。这些发现的含义以及我们的基本假设是，在患有牙周附着丧失和炎症的患者中，口腔微生物可能会在人类体内诱导出抗PC抗体，这些抗体可能会影响PAF依赖的生物活性。我们建议研究人抗PC抗体对这些功能的影响，包括IgG2的产生、细胞因子的释放和PMN的迁移。同样有趣的是，肺炎链球菌利用其PC抗原模拟PAF分子进入循环，进入和迁移内皮细胞。我们的初步数据表明，口服抗原模拟PAF分子并进入和转运内皮细胞。我们的初步数据表明，口腔细菌，如血链球菌、放线菌、伴生放线菌和核杆菌也可能利用这一途径。这可能解释了牙周炎患者体内高水平的抗PC抗体。此外，通过这一途径进入循环的能力在增加心内膜炎和心血管疾病的风险方面可能很重要。因此，我们建议进一步研究人类抗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.