ANTIBODY REACTIVITY TO PHOSPHORYLCHOLINE

磷酸胆碱抗体反应性

• 批准号: 6473494
• 负责人: HARVEY Allen SCHENKEIN
• 金额: $ 14.05万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6473494
• 关键词: Actinobacillus actinomycetemcomitans; Actinomyces; Bacteroides gingivalis; Fusobacterium nucleatum; Streptococcus sanguis; affinity chromatography; antibody formation; antigen antibody reaction; bacterial cytopathogenic effect; bactericidal immunity; blood chemistry; clinical research; cytokine; dental disorder chemotherapy; electron microscopy; enzyme linked immunosorbent assay; fluorescence microscopy; genetic regulation; human subject; immunoglobulin G; immunoglobulin M; intracellular transport; laboratory rabbit; linkage mapping; oral bacteria; oral pharyngeal surgery; periodontitis; phosphorylcholine; platelet activating factor; statistics /biometry; tissue /cell culture; transmission electron microscopy; western blottings

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.

项目 5：人类抗体对磷酸胆碱的反应性：PAR 依赖性生物活性的调节、携带磷酸胆碱的牙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却知之甚少。据认为，大多数人类抗 PC 反映了之前接触过肺炎链球菌，但这种针对肺炎链球菌感染的反应的保护性质值得怀疑。我们发现，牙周附着丧失患者的人类抗 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、放线菌以及具核梭杆菌、嗜空杆菌和伴随放线菌菌株，都具有含 PC 的抗原。我们的初步研究还表明，人类抗 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。这些发现和我们的基本假设的含义是，牙周附着丧失和炎症患者的口腔微生物可能会在人体中诱导抗 PC 抗体，并且这些抗体可能影响 PAF 依赖性生物活性。我们建议检查人抗 PC 对这些功能的影响，包括 IgG2 产生、细胞因子释放和 PMN 迁移。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可以模仿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，如血链球菌、放线菌、A. actinomycetemcomitans 和 F. nucleatum 也可能利用此途径。这或许可以解释牙周炎患者体内抗 PC 水平较高的原因。此外，通过该途径进入循环的能力对于增加心内膜炎和心血管疾病的风险可能很重要。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。