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16名研究人员在四个项目和两个核心继续我们的工作在该地区的联系慢性感染（M。肺炎）和慢性哮喘。最近有许多出版物表明，在哮喘患者的亚组中，约50%具有相关的非典型细菌过程。 因此，本PPG将重点关注M。肺炎-哮喘相互作用 项目1将评估M. pneumoniae对诱导成纤维细胞增殖和改变气道结构（重塑）和功能的神经源性炎症的作用。 这将使用哮喘气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，第一道气道防御机制和M的相互作用。肺炎。 该项目还将确定炎症反应放大所需的蛋白质结构域。 除了该体外工作外，小鼠体内工作将确定SP-A和SP-D如何调节支原体反应。 项目3将使用支原体诱导的慢性“哮喘样”状态的小鼠模型，该模型由过敏原和感染暴露的相互作用引起。 该模型将用于了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M.肺炎对肥大细胞功能的影响。 每个项目都是互补和互动的，因此，科学家的临界质量将能够通过PPG在更高的互动水平上工作。 行政核心将作为项目的支点，组织学和微生物学核心将为每个项目服务。 目的是了解M.肺炎和哮喘的研究将通过该PPG获得，并最终为理解哮喘病理生理学和潜在的未来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.