PULMONARY DEFENSES: ROLE OF LUNG MACROPHAGE MOTILITY

这些研究的目的是研究它们的运动特性 肺泡巨噬细胞以及这些细胞的运动行为 与清除肺部细菌有关。这些研究 分为两部分。首先，使用线性琼脂糖下 迁移试验，我们将测量趋化运动和趋化 描述固有单元属性的参数术语， 并测试这些肺巨噬细胞的运动特性 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, 使用细胞群体，我们将测量随机的运动性 趋化系数和趋化系数。二、能动性 将用延时视频记录单个单元的 用显微镜来确定细胞速度、持久性等变量 时间和方向偏向。这两种方法都将用于 确定他们彼此之间以及与 对理论模型的预测。此外，这些内在的 运动参数也将与某些结构相关 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这一假设 趋化性在清除肺部细菌方面很重要。 使用肺清除的数学模型，我们已经检查了 之前公布的数据显示，相当程度的 肺泡巨噬细胞趋化能力是必需的 观察到的清除率。我们现在将检验这一假设 在老鼠身上进行实验。使用测量的运动性 上一节中派生的变量，我们将确定如何 肺部细菌清除的理论模型符合 肺清除量的实验观察值。为了进一步 测试该模型，我们将测量肺的运动参数 巨噬细胞暴露于高氧后(体内和体外)。 从细菌清除量预测的变化 裸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。

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.