In Vitro and in Vivo Lung Studies

体外和体内肺研究

• 批准号: 7556205
• 负责人: MICHAEL A. MATTHAY
• 金额: $ 12.15万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-25 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7556205
• 关键词: Acids; Alveolar; Animals; Condition; Cultured Cells; Data; Epithelial; Epithelial Cells; Human; In Vitro; Injury; Lung; Modeling; Mus; Organism; Pathologic; Pseudomonas; Pseudomonas aeruginosa; Purpose; Rattus; Research; Respiratory physiology; Rodent; Stimulus; Structure; Testing; Transferase; Type II Epithelial Receptor Cell; Work; design; experience; in vivo; lung injury; matrigel; novel; programs; research study

This Cell Culture and Animal Core is designed to support specific aims in each of the 4 projects in this revised Program Project Application. There are two specific aims. The first aim is to supply alveolar epithelial type II cells from human lungs, rat lungs, and mouse lungs to support the specific aims of Project 1 (Mostov), Project 2 (Engel), and Project 3 (Rosen). Our research group has had extensive experience in isolating, culturing, and studying pulmonary alveolar epithelial type II cells from human and rodent lungs under both normal and pathological conditions. This work has been especially productive in studying mechanisms of alveolar epithelial injury from P.aeruginosa ExoT and ExoS as well as establishing how the ADP ribosyl transferase domain of P.aeruginosa ExoT contributes to the biologic activities of the Pseudomonas organisms (Project 2, Engel). In addition, our recent work has established that human alveolar epithelial type II cells can be cultured in matrigel and induced to form 3-dimentional structures that resemble authentic alveolar-like structures. This accomplishment provides a major opportunity for novel studies of lung epithelial function under normal and pathologic conditions (Project 1, Mostov). The second aim of this core, which represents an expanded direction, is to carry out in vivo mouse studies using pathologic models of lung injury to test specific hypotheses in Project 3 (Rosen) and Project 4 (Werb). These in vivo mouse experiments will use both infectious and non-infectious stimuli to test the effects on lung function and overall survival. Our research group has extensive experience with in vivo studies and there is considerable preliminary data that has been generated in testing specific hypotheses that a part of Project 3 (Rosen) and Project 4 (Werb).

这种细胞培养和动物核心旨在支持在这四个项目中的每个项目中的特定目标 修订程序项目申请。有两个具体的目标。第一个目的是提供牙槽上皮 来自人肺，大鼠肺和小鼠肺的II型细胞，以支持项目1（Mostov）， 项目2（恩格尔）和项目3（罗森）。我们的研究小组在隔离， 培养和研究来自人类和啮齿动物肺的肺肺泡上皮II型细胞 正常和病理状况。这项工作在研究机制方面尤其有效 P.Aeruginosa Exot和Exos的肺泡上皮损伤，并确定ADP核糖基如何 P.Aeruginosa Exot的转移酶结构域有助于假单胞菌的生物学活性 有机体（项目2，恩格尔）。此外，我们最近的工作已经确定了人类肺泡上皮 II型细胞可以在母质中培养，并诱导形成类似于真实的三维结构 牙槽样结构。这项成就为肺的新颖研究提供了重要的机会 正常和病理条件下的上皮功能（项目1，Mostov）。这个核心的第二个目标， 代表扩展方向的，是使用病理模型进行体内小鼠研究 在项目3（Rosen）和项目4（WERB）中测试特定假设的肺损伤。这些体内鼠标 实验将使用传染性和非感染性刺激来测试对肺功能和整体的影响 生存。我们的研究小组在体内研究方面拥有丰富的经验，并且有很多 在测试项目3（Rosen）和 项目4（WERB）。