PULMONARY DEFENSES: ROLE OF LUNG MACROPHAGE MOTILITY

肺防御：肺巨噬细胞活力的作用

• 批准号: 3361413
• 负责人: RONALD P DANIELE
• 金额: $ 17.01万
• 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/3361413
• 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.

这些研究的目的是调查运动特性 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，使用线性琼脂糖下 迁移试验，我们将测量趋化和趋化性， 表征固有细胞特性的参数的术语， 测试肺巨噬细胞的运动特性 符合细胞迁移的理论模型（来源于 Fick定律）。 将使用两种实验方法。 第一、 使用细胞群，我们将测量随机运动性， 系数和趋化性系数。 第二，运动性 每一个细胞都将被延时录像记录下来 显微镜来确定变量，如细胞速度，持久性 时间和方向偏差。 这两种方法将用于 确定他们彼此之间以及与 理论模型的预测。 此外，这些内在的 运动参数也将与某些结构有关 参与细胞的运动器官-细胞骨架 系统 这些研究的第二部分将检验假设， 趋化性在从肺清除细菌中是重要的。 使用肺清除率的数学模型，我们已经检查了 此前公布的数据显示， 需要肺泡巨噬细胞趋化能力来解释 观察到的清除率。 我们现在要验证这个假设 在老鼠身上做实验。 使用测量的运动 在上一节中导出的变量，我们将确定如何 肺部细菌清除的理论模型与 肺清除率的实验观察值。 进一步 对该模型进行测试，测量肺的运动参数 巨噬细胞暴露后（体内和体外）高氧。 根据细菌清除率预测的细菌清除率变化 暴露细胞的测量参数和理论模型将 然后与实验观察到的 高氧后的细菌清除。