The Effect of Mycoplasma on Chronic Asthma

描述(由申请人提供)： 这项计划项目赠款(PPG)将汇集四个项目和两个核心的16名研究人员，继续我们在慢性感染(肺炎支原体)和慢性哮喘之间的联系方面的工作。最近有许多文献表明，在哮喘患者的一个亚组中，大约50%有相关的非典型细菌过程。因此，本PPG将侧重于肺炎支原体与哮喘的相互作用。 项目1将评估肺炎支原体在神经源性炎症、诱导成纤维细胞增殖和改变呼吸道结构(重塑)和功能方面的作用。这将使用哮喘的呼吸道上皮细胞和组织来完成。项目2的重点是研究表面活性蛋白(SP)-A和-D、一线呼吸道防御机制和肺炎支原体之间的相互作用。该项目还将确定放大炎症反应所需的蛋白质结构域。除了这项体外工作外，在小鼠体内的工作将确定SP-A和SP-D如何调节支原体的反应。项目3将使用支原体引起的慢性“类哮喘”状态的小鼠模型，这种状态是由过敏原和感染暴露相互作用造成的。该模型将被用来理解慢性支气管高反应性和气道重塑的发展。项目4将使用人类上皮细胞系来研究肺炎支原体对肥大细胞功能的影响。 每个项目都是互补性和互动性的，因此，关键的科学家群体将能够通过PPG在更高和互动的水平上工作。行政核心将作为项目的支点，组织病理学和微生物学核心将为每个项目服务。 了解肺炎支原体和哮喘之间的相互作用的目标将通过这一PPG获得，并最终将为理解哮喘的病理生理学和未来潜在的新疗法提供新的知识。

DESCRIPTION (provided by applicant): This Program Project Grant (PPG) will bring together 16 investigators in four Projects and two Cores to continue our work in the area of the link between chronic infection (M. pneumoniae) and chronic asthma. There have been numerous recent publications suggesting that in a subgroup of asthmatics, approximately 50% have an associated atypical bacterial process. Thus, this PPG will focus on the M. pnemoniae-asthma interaction. Project 1 will evaluate the effect of M. pneumoniae on neurogenic inflammation inducing fibroblast proliferation and altering airway structure (remodeling) and function. This will be done using asthmatic airway epithelial cells and tissue. The focus of Project 2 is to examine the interactions of surfactant proteins (SP)-A and -D, the first line airway defense mechanisms and M. pneumoniae. This project will also identify the domains of the protein that are required for the amplification of the inflammatory response. In addition to this in vitro work, in vivo mouse work will determine how the mycoplasma response is modulated by SP-A and SP-D. Project 3 will use a mouse model of a mycoplasma induced chronic "asthma-like" state by the interaction of allergen and infection exposures. This model will be used to understand the development of chronic bronchial hyper-responsiveness and airway remodeling. Project 4 will use an epithelial human cell line to investigate the effects of M. pneumoniae on mast cell function. Each project is complementary and interactive, thus the critical mass of scientists will be able to work at a higher and interactive level through the PPG. The Administrative Core will function as the fulcrum for the projects and the Histopathology and Microbiology Core will serve each project. The goal of understanding the interaction between M. pneumoniae and asthma will be obtained through this PPG and will ultimately give new knowledge to the understanding of asthma pathophysiology and potential future novel therapies.