COLLECTINS AND LUNG DEFENSE

本申请试图确定病毒感染的影响 表面活性物质动态平衡及表面活性蛋白A的作用 在保护肺部免受病毒感染方面。肺是持续不断的 暴露在吸入的病原体中，然而，仍然显著地没有 感染。SP-A是一种丰富的肺选择性集合素，由 呼吸道上皮细胞，并在呼吸道内分泌。SP-A的体外培养 增强对微生物病原体的吞噬和杀灭作用。直接 确定SP-A在体内、基因靶向缺失SP-A(SP-A)小鼠中的作用 A-/-)被生成。SP-A(-/-)小鼠对细菌敏感 感染。目前的应用测试了病毒的假设 感染改变表面活性物质磷脂和蛋白质浓度 SP-A通过保护肺免受体内病毒感染 呼吸道上皮细胞感染与增强吞噬功能 调节肺泡巨噬细胞的自由基合成。至 确定SP-A在肺防御中的作用，实验将确定 SP-A对呼吸道合胞病毒(RSV)的体内保护作用 感染。为了确定SP-A调节的病毒清除机制， RSV的吞噬作用和氧、氮自由基的产生 肺泡巨噬细胞将在有无SP的情况下进行评估 答：这项申请将确定角色和描述机制 通过SP-A提供先天免疫来预防RSV感染。是这样的 这些数据可能在未来的治疗和预防设计中有用 易感人群中病毒性肺炎的风险。 这项提案的首席调查员已经完成了一项研究 他目前是重症监护医学的研究讲师 儿科，肺生物科。贯穿她的整个过程 在训练中，她表现出了持续的兴趣和能力 完成基础科学研究。RCA将允许PI 继续在研究环境中发展，并取得了许多成功 独立调查人员专注于肺部基础科学和 临床研究。该方案的实验设计包括 具有挑战性，但特别是在这种环境下，可实现的目标 将为认识急性肺病提供重要的知识 肺的损伤和宿主防御。

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.