ANTIBODY REACTIVITY TO PHOSPHORYLCHOLINE

项目五：人抗体对磷酸胆碱的反应性：PAR依赖性生物学活性的调节，含磷酸胆碱菌斑细菌的诱导，以及与牙周破坏的关系。对磷酸胆碱（PC）的抗体反应已被广泛研究，但其在人类中的生物学意义知之甚少。人们认为，大多数人抗PC抗体反映了先前对S. pneumoniae感染，但这种反应的保护性质对S. pneumoniae是可疑的。我们已经发现，人抗PC水平显着较高的患者谁经历了牙周附着损失比健康受试者。此外，我们的初步数据和其他研究小组的最新数据表明，许多牙菌斑细菌物种，包括几种链球菌，放线菌和F。nucleatum，H. aphrophilus和A.伴放线菌携带含PC的抗原。我们的初步研究还表明，人抗PC反应与脂质介质血小板活化因子（PAF）。在研究中，我们试图了解PC深刻抑制IgG 2的生产机制，PAF受体拮抗剂也是如此。这些发现和我们的基本假设的含义是，在患有牙周附着丧失和炎症的患者中，抗PC抗体可能由口腔微生物在人体中诱导，并且这些抗体可能影响PAF依赖性生物活性。我们建议研究人抗PC对这些功能的影响，包括IgG2的产生，细胞因子的释放和PMN的迁移。同样令人感兴趣的是S.肺炎克雷伯氏菌通过利用其PC抗原模拟PAF分子进入循环，并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分子并进入和迁移内皮细胞。我们的初步数据表明，口腔细菌，如S。sanguis、放线菌A. actinomycetemcomitans和F.核质也可以利用这一途径。这可能解释了牙周炎患者中高水平的抗PC。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.