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.

本应用旨在确定病毒感染的影响 在表面活性剂稳态和表面活性剂蛋白A（SP-A）的作用上 在保护肺部免受病毒感染免受病毒感染。肺部不断 暴露于吸入的病原体，但仍然明显地摆脱了 感染。 SP-A是由 呼吸道上皮，在气道中分泌。 体外SP-A 增强的吞噬作用和微生物病原体的杀戮。 直接 确定sp-a在体内的作用，基因靶向缺乏sp-a的小鼠（sp- A - / - ）生成。 SP-A（ - / - ）小鼠容易受到细菌的影响 感染。 目前的申请检验了病毒的假设 感染改变表面活性剂磷脂和蛋白质浓度，以及 SP-A通过保护通过保护肺免受体内病毒感染 感染并增强吞噬作用的呼吸道上皮细胞 并通过肺泡巨噬细胞调节自由基的合成。 到 确定SP-A在肺防御中的作用，实验将确定 如果SP-A保护体内小鼠免受呼吸综合病毒（RSV）的影响 感染。 为了确定由SP-A调节的病毒清除机制， RSV吞噬作用以及氧和氮自由基的产生 在存在和不存在SP-的情况下，将评估肺泡巨噬细胞 答：该应用将确定角色并描述机制 SP-A提供了先天免疫，以防止RSV感染。 这样的 在设计治疗和预防方面，数据可能会很有用 易感患者的病毒性肺炎。 该提案的主要调查员已完成奖学金 在重症监护医学中，目前是 儿科系肺生物学系。 整个她 培训，她表现出对的持续兴趣和能力 完成基础科学调查。 RCA将允许PI 继续在许多成功的研究环境中发展 独立研究人员专注于肺基础科学和 临床研究。 该提案的实验设计包括 具有挑战性，但尤其是在这种环境下，可以实现的目标 将为急性肺的理解提供重要的知识 受伤和霍斯肺的防御。