Role of Surfactant in Mycoplasma Pulmonary Infection and Exacerbation

描述（由申请人提供）：假设：本提案中待检验的总体假设是SP-A在肺宿主防御M中起重要的保护作用。肺炎（MP）感染和气道反应性的调节从先天性到适应性免疫的转变。具体目的：（1）探讨SP-A在调节DC成熟和M.（2）确定SP-A是否作为调理素并有助于M.通过未成熟DC和肺泡巨噬细胞抑制肺炎支原体，从而增加清除率，同时减少上皮结合和对宿主的损伤;（3）检查SP-A对M.使用SP-A缺陷的小鼠研究肺炎诱导的气道过度活跃，以更好地理解SP-A在实验性哮喘环境中的作用。研究设计：SP-A在调节MP诱导的DC成熟和细胞因子调节中的作用将首先通过研究从野生型和SP-A缺失小鼠培养的骨髓来源的树突状细胞来检查。然后使用感染M的SP-A缺陷小鼠评估这些参数。肺炎。我将进行更全面的实验，检查MP清除，摄取和上皮损伤，并确定SP-A是否介导这些活动。使用患有实验性过敏性哮喘的SP-A缺失小鼠的实验将用于研究SP-A在MP诱导的哮喘恶化中的作用。相关性：过敏原、感染和哮喘之间的关系包括从已确立疾病的恶化到疾病的发展和持续的范围。先天免疫系统和适应性免疫系统之间的相互作用可能是最终决定哮喘表型的关键。表面活性剂蛋白在哮喘中尚未得到广泛研究，但已知其在宿主防御和炎症调节中发挥重要作用，这可能有助于哮喘的发展和持续。本研究将有助于阐明表面活性蛋白A在M.肺炎性肺部感染，特别是与哮喘相关的症状。

DESCRIPTION (provided by applicant): Hypothesis: The overall hypothesis to be tested in this proposal is that SP-A plays an important protective role in pulmonary host defense against M. pneumoniae (MP) infections and airway reactivity by modulating the transition from innate to adaptive immunity. Specific Aims: (1) to investigate the role of SP-A in regulating DC maturation and cytokine modulation in response to M. pneumoniae infection in vitro; (2) to determine if SP-A acts as an opsonin and aids in the uptake of M. pneumoniae by immature DCs and alveolar macrophages, thereby increasing clearance while decreasing epithelial binding and insult to the host; (3) to examine the effects of SP-A on M. pneumoniae induced airway hyperactivity using mice deficient in SP-A to better understand the role of SP-A in an experimental asthma setting. Study Design: The role of SP-A in regulating MP-induced DC maturation and cytokine modulation will first be examined by studying bone marrow derived dendritic cells cultured from wild type and SP-A null mice. These parameters will then be assessed using mice deficient in SP-A infected with M. pneumoniae. I will perform more comprehensive experiments examining MP clearance, uptake and epithelial damage and determine if SP-A mediates these activities. Experiments using SP-A null mice with experimental allergic asthma will be used to study the role of SP-A in MP induced asthma exacerbations. Relevance: The relationship between allergen, infection and asthma comprises a spectrum ranging from exacerbation of established disease to development and persistence of disease. The interactions between the innate and adaptive immune systems may be pivotal in ultimately determining the phenotypic presentation of asthma. Surfactant proteins have not been widely studied in asthma but are known to play important roles in host defense and modulation of inflammation which may contribute to the development and persistence of asthma. The research proposed in this project will aid in elucidating the role of Surfactant Protein-A in M. pneumoniae pulmonary infections specifically associated with asthma related symptoms.