Role of unique ADP-ribosylating vacuolating Mycoplasma pneumoniae toxin in asthma

独特的 ADP-核糖基化空泡肺炎支原体毒素在哮喘中的作用

• 批准号: 7914874
• 负责人: JOEL Barry BASEMAN
• 金额: $ 40.79万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-12 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7914874
• 关键词: Role; unique; ADP; ribosylating; vacuolating

The San Antonio/Dallas Asthma and Allergic Diseases Cooperative Research Center represents an integrative, collaborative and innovative multidisciplinary effort to investigate the role of a unique Mycoplasma pneumonias toxin in asthma and related airway diseases. This toxin, designated Community Acquired Respiratory Distress Syndrome Toxin (CARDS TX) remarkably replicates the proinflammatory cytokine/chemokine profiles and histopathology that accompany M. pneumoniae infection. This consortium between The University of Texas Health Science Center at San Antonio and The University of Texas Southwestern Medical School in Dallas combines 4 projects, which focus on basic, clinical and animal modeling strategies, with 2 support cores (administrative and pathology) to bring a totally new approach to defining the relationship between M. pneumoniae and the pathogenesis of asthma. A substantial literature, which has accumulated over thirty-five years, connects M. pneumoniae to onset, exacerbation, and chronicity of asthma, yet no single mycoplasma virulence determinant, or mycoplasma molecule for that matter, has been shown to be a mediator of symptoms and associated pathologies. This lack of definable M. pneumoniae pathogenic factors has greatly hampered an understanding of how M. pneumoniae influences the development and progression of airway diseases. This is especially challenging in complex diseases like asthma, where genetic, immunologic, infectious and environmental variables appear to affect disease development and progression. A major focus of the AADCRC is to directly link the biochemical, molecular and immunological properties of the ADP-ribosylating, vacuolating M. pneumoniae CARDS TX (Project 4), to diagnosis and treatment of asthmatic patients (Projects 3 and 4). By so doing, we hope to demonstrate that CARDS TX is a key mediator of asthma-associated pathobiology in humans (Project 3) and in experimentally infected or intoxicated mice (Projects 1 and 2). Therefore, we intend to (a) directly connect CARDS TX to asthma pathogenesis through novel and effective CARDS TX-targeted diagnostic assessments (ELISA, immunohistochemistry, antigen capture and PCR methodologies) using patient's nasal lavage, sputum and serum samples; (b) use mouse models of M. pneumoniae infection and CARDS TX intoxication to examine both acute and chronic stages of asthma and therapeutic interventions as well as the impact of CARDS TX on airway hyper-reactivity; and (c) further characterize ADP-ribosylating activities of CARDS TX and develop effective and rapid diagnostics to assist in the treatment and control of asthma and related pathologies. The key investigators of each project and core have strong track records and expertise in asthma, airway-related pathologies, immunopathogenesis and M. pneumoniae biology and virulence as well as a history of collaboration and co-publication.

圣安东尼奥/达拉斯哮喘和过敏性疾病合作研究中心代表了一个综合性， 协作和创新的多学科努力，以调查独特的支原体肺炎的作用 哮喘和相关气道疾病中的毒素。这个毒素，指定的社区获得了呼吸窘迫 综合征毒素（Cards TX）明显复制促炎性细胞因子/趋化因子曲线和 肺炎支原体感染的组织病理学。德克萨斯大学之间的这个财团 圣安东尼奥的健康科学中心和达拉斯的德克萨斯大学西南医学院 结合了4个项目，这些项目侧重于基本，临床和动物建模策略，并与2个支持核心 （行政和病理）为定义M之间的关系带来一种全新的方法。 肺炎和哮喘发病机理。大量文献，已经积累了三十五 几年，将肺炎麦芽孢菌连接到发作，加剧和哮喘的慢性病，​​但没有单一的支原体 毒力决定因素或支原体分子已被证明是症状的介体 和相关的病理。这种缺乏可定义的肺炎肺炎菌致病因素已极大地阻碍了 了解肺炎支原体如何影响气道疾病的发展和发展。这是 在哮喘等复杂疾病中尤其具有挑战性，遗传，免疫学，传染性和 环境变量似乎会影响疾病的发展和进展。 AADCRC的主要重点是 直接连接ADP-核糖基化的生化，分子和免疫学特性。 肺炎卡TX（项目4），诊断和治疗哮喘患者（项目3和4）。由此 这样做，我们希望证明卡片TX是人类哮喘相关病原体学的关键调解人 （项目3）以及在实验感染或陶醉的小鼠中（项目1和2）。因此，我们打算（a） 直接通过新颖有效的卡片将卡片TX连接到哮喘发病机理TX靶向诊断 使用患者的鼻腔评估（ELISA，免疫组织化学，抗原捕获和PCR方法） 灌洗，痰液和血清样品； （b）使用M.肺炎感染和卡片的鼠标模型TX 中毒以检查哮喘和治疗干预措施的急性和慢性阶段 卡TX对气道高反应性的影响； （c）进一步表征ADP-核糖基化活性 卡TX并开发有效而快速的诊断，以协助治疗和控制哮喘和控制 相关病理。每个项目和核心的主要调查人员都具有强大的记录和专业知识 哮喘，与气道相关的病理，免疫致病发生和肺炎支原体生物学和毒力以及A 协作和共出版的历史。