ANTIBODY REACTIVITY TO PHOSPHORYLCHOLINE

磷酸胆碱抗体反应性

• 批准号: 6954494
• 负责人: HARVEY Allen SCHENKEIN
• 金额: $ 17.46万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6954494
• 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; lectin; 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：对磷酸胆碱的人类抗体反应性：对分子依赖性生物学活性的调节，磷酸胆碱轴承斑块细菌的诱导以及与牙周破坏的关系。对磷酸胆碱（PC）的抗体反应已经进行了广泛的研究，但其在人类中的生物学意义知之甚少。人们认为，大多数人类抗PC反映了先前暴露于肺炎链球菌，但是这种反应抵抗肺炎链球菌感染的保护性值得怀疑。我们发现，经历牙周附着损失的患者的人类抗PC水平明显高于健康受试者。此外，我们的初步数据和来自其他组的最新数据表明，许多牙菌菌种类，包括几种链球菌，放线菌和F. nucleatum，H。aphrophilus和A.a。stecinomycetemcetemitans携带PC抗原的抗原。我们的初步研究还表明，人类抗PC与脂质介体血小板激活因子（PAF）反应。在我们试图理解机制的研究中，PC和PAF受体拮抗剂也强烈抑制了IgG2的产生。这些发现的含义以及我们的基本假设是，在牙周附着损失和炎症的患者中，口服微生物可能会诱导抗PC抗体，并且这些抗体可能会对PAF依赖性生物学活性产生影响。我们建议检查人类抗PC对此类功能的影响，包括IgG2产生，细胞因子释放和PMN迁移。肺炎链球菌通过利用其PC抗原模仿PAF分子并进入和迁移的内皮细胞来访问循环。我们的初步数据表明，口服抗原模拟PAF分子并进入和移民内皮细胞。我们的初步数据表明，口服细菌，例如sanguis，放线菌，A。stinomycetemcomitans和F. nutleatum也可以使用此途径。这可能解释了牙周炎患者中高水平的抗PC。此外，通过该途径进入循环的能力对于促进心内膜炎和心血管疾病的风险很重要。因此，我们建议进一步研究人类抗PC反应的生物学意义，以及口服细菌利用PC进入循环的可能性。