PULMONARY DEFENSES: ROLE OF LUNG MACROPHAGE MOTILITY

肺防御：肺巨噬细胞活力的作用

• 批准号: 3361414
• 负责人: RONALD P DANIELE
• 金额: $ 16.82万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3361414
• 关键词: alveolar macrophages; bactericidal immunity; cell migration; cell population study; chemotaxis; cinemicrography; cytoskeleton; density gradient ultracentrifugation; diagnostic respiratory lavage; laboratory rat; mathematical model; model design /development; respiratory airway clearance

The goal of these studies is to investigate the motile properties of alveolar macrophages and how the motile behavior of these cells is related to the clearing of bacteria from the lungs. The studies are divided into two parts. First, using the linear under-agarose migration assay, we will measure chemokinesis and chemotaxis in terms of parameters that characterize intrinsic cell properties, and test how well these motile properties of lung macrophages conform to a theoretical model of cell migration (derived from Fick's law). Two experimental approaches will be used. First, using populations of cells, we will measure the random motility coefficient and the chemotaxis coefficient. Second, the motility of individual cells will be recorded with time-lapse video microscopy to determine variables such as cell speed, persistence time and orientation bias. Both approaches will be used to determine how well they agree with each other and with the predictions of the theoretical model. In addition, these intrinsic motile parameters will also be related to certain structures involved in the cell's locomotor apparatus - the cytoskeletal system. The second part of these studies will test the hypothesis that chemotaxis is important in the clearance of bacteria from the lung. Using a mathematical model of lung clearance, we have examined previously published data and shown that a significant degree of alveolar macrophage chemotactic ability is required to account for the observed clearance rate. We will now test this hypothesis experimentally in the rat. With the use of measured motile variables derived in the previous section, we will determine how well the theoretical model of lung bacterial clearance agrees with the experimentally observed values of lung clearance. To further test this model, we will measure the motile parameters of lung macrophages after exposure (in vivo and in vitro) to hyperoxia. The changes in bacterial clearance that are predicted from the measured parameters of exposed cells and the theoretical model will then be compared to the experimentally observed alterations in bacterial clearance after hyperoxia.

这些研究的目的是研究运动特性 肺泡巨噬细胞的变化以及这些细胞的运动行为 与肺部细菌的清除有关。 研究 分为两部分。 首先，使用线性琼脂糖 迁移测定，我们将测量趋化作用和趋化性 表征细胞内在特性的参数术语， 并测试肺巨噬细胞的这些运动特性 符合细胞迁移的理论模型（源自 菲克定律）。 将使用两种实验方法。 第一的， 使用细胞群，我们将测量随机运动 系数和趋化系数。 二、机动性 将用延时视频记录单个细胞的情况 显微镜确定细胞速度、持久性等变量 时间和方向偏差。 这两种方法都将用于 确定他们彼此之间以及与对方的一致程度 理论模型的预测。 此外，这些内在的 运动参数也与某些结构有关 参与细胞的运动装置 - 细胞骨架 系统。 这些研究的第二部分将检验以下假设： 趋化性对于从肺部清除细菌很重要。 使用肺清除率的数学模型，我们检查了 先前公布的数据表明，在很大程度上 需要考虑肺泡巨噬细胞的趋化能力 观察到的清除率。 我们现在将检验这个假设 在大鼠身上进行实验。 随着使用测量的运动 在上一节中导出的变量，我们将如何确定 肺部细菌清除的理论模型与 实验观察到的肺清除率值。 为了进一步 测试这个模型，我们将测量肺的运动参数 暴露于高氧（体内和体外）后的巨噬细胞。 根据预测的细菌清除率的变化 暴露细胞的测量参数和理论模型将 然后与实验观察到的变化进行比较 高氧后细菌清除。