COLLECTINS AND LUNG DEFENSE

集合素和肺部防御

• 批准号: 6627298
• 负责人: ANN MARIE LEVINE
• 金额: $ 12.42万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627298
• 关键词: alveolar macrophages; gene targeting; genetically modified animals; immunity; laboratory mouse; pathologic process; phagocytosis; pulmonary surfactants; respiratory epithelium; respiratory infections; respiratory syncytial virus

The present application seeks to determine the effect of viral infection on surfactant homeostasis and the role of surfactant protein-A (SP-A) in protecting the lung from viral infection. The lung is continually exposed to inhaled pathogens, yet, remains remarkably free from infection. SP-A is an abundant lung selective collectin produced by the respiratory epithelium and secreted in the airway. In vitro SP-A enhanced phagocytosis and killing of microbial pathogens. To directly determine the role of SP-A in vivo, gene targeted mice lacking SP-A (SP- A-/-) were generated. SP-A (-/-) mice are susceptible to bacterial infection. The present application tests the hypothesis that viral infection alters surfactant phospholipid and protein concentrations and SP-A protects the lung from viral infection in vivo by protecting respiratory epithelial cells from infection and enhancing phagocytosis and modulating synthesis of free radicals by alveolar macrophages. To determine the role of SP-A in lung defense, experiments will determine if SP-A protects mice in vivo from respiratory syncytial virus (RSV) infection. To determine viral clearance mechanisms modulated by SP-A, RSV phagocytosis and generation of oxygen and nitrogen radicals by alveolar macrophages will be assessed in the presence and absence of SP- A. This application will determine the role and delineate mechanisms by which SP-A provides innate immunity to prevent RSV infections. Such data may be useful in the future in designing treatment and prevention of viral pneumonia in susceptible patients. The principle investigator for this proposal has completed a fellowship in critical care medicine and is currently a Research Instructor in the Division of Pulmonary Biology, Department of Pediatrics. Throughout her training, she has demonstrated a continued interest in and ability to accomplish basic science investigation. The RCA will allow the PI to continue to develop in a research environment with many successful independent investigators focused to pulmonary basic science and clinical research. The experimental design on this proposal includes challenging but, particularly in this environment, achievable goals that will provide important knowledge to the understanding of acute lung injury and host defense of the lung.

本申请试图确定病毒感染对细胞的影响， 表面活性物质稳态和表面活性蛋白-A（SP-A）的作用 保护肺部免受病毒感染肺持续 暴露于吸入的病原体，然而，仍然显着没有从 感染 SP-A是一种丰富的肺选择性聚集素，由肺巨噬细胞产生， 呼吸道上皮细胞和分泌的气道。 体外SP-A 增强的吞噬作用和杀死微生物病原体。 直接 确定SP-A在体内的作用，缺乏SP-A的基因靶向小鼠（SP-A） A-/-）。 SP-A（-/-）小鼠对细菌易感 感染 本申请测试了病毒性的 感染改变表面活性剂磷脂和蛋白质浓度， SP-A在体内通过保护肺免受病毒感染， 呼吸道上皮细胞免受感染并增强吞噬作用 以及调节肺泡巨噬细胞的自由基合成。 到 为了确定SP-A在肺防御中的作用，实验将确定 如果SP-A在体内保护小鼠免受呼吸道合胞病毒（RSV）的侵害， 感染 为了确定SP-A调节的病毒清除机制， RSV吞噬作用和氧和氮自由基的产生 将在存在和不存在SP的情况下评估肺泡巨噬细胞。 A. 此应用程序将确定角色并描述机制 SP-A通过其提供先天免疫以防止RSV感染。 等 这些数据在未来设计治疗和预防措施时可能会很有用。 病毒性肺炎的发病率 该提案的主要研究员已完成研究金 在重症监护医学，目前是一个研究导师在 小儿科肺生物学室。 在她的整个 培训，她表现出持续的兴趣和能力， 完成基础科学研究。 RCA将允许PI 继续在研究环境中发展， 专注于肺部基础科学的独立研究人员， 临床研究 本方案的实验设计包括 具有挑战性，但特别是在这种环境下， 将为了解急性肺提供重要知识 肺的损伤和宿主防御。