Fisher E S, Lauffenburger D A
Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104-6393.
Math Biosci. 1990 Feb;98(1):73-102. doi: 10.1016/0025-5564(90)90012-n.
White blood cells of the immune system must encounter specific targets such as bacteria, malignant cells, virus-infected cells or other cells of the immune response in order to carry out their function of protecting the host from infectious and malignant disease. To analyze the dynamics of this process, a mathematical model has been developed for elimination of proliferating targets by a constant population of motile immune system cells in two dimensions. Encounter is assumed to be the rate-limiting step for elimination. This model makes use of a previously derived analysis of single cell-target encounter times, which yields an encounter rate constant that is incorporated into a kinetic conservation equation for target number density. This paper focuses on the influence of directed cell movement, or chemotaxis, as well as other cell motility properties, such as cell speed and persistence, on target elimination dynamics. A particularly significant result is that a given relative decrease in chemotactic responsiveness leads to much more severe deficiencies in target clearance rates for low levels of baseline chemotactic responsiveness than for high levels of baseline responsiveness. The general model results are then applied to the particular example of bacterial clearance from the lung surface by alveolar macrophages. It is shown that moderate levels of macrophage chemotactic responsiveness, similar to those measured in vitro, can account for the experimentally observed rates of bacterial elimination from the lung for typical values of bacterial specific growth rate and alveolar macrophage number density.
免疫系统的白细胞必须遇到特定目标，如细菌、恶性细胞、病毒感染细胞或免疫反应中的其他细胞，才能执行其保护宿主免受感染性和恶性疾病侵害的功能。为了分析这一过程的动态变化，已经建立了一个数学模型，用于二维空间中恒定数量的运动免疫系统细胞对增殖目标的清除。相遇被认为是清除的限速步骤。该模型利用了先前对单细胞与目标相遇时间的分析，得出一个相遇速率常数，并将其纳入目标数量密度的动力学守恒方程。本文重点研究定向细胞运动（即趋化性）以及其他细胞运动特性（如细胞速度和持续性）对目标清除动态的影响。一个特别显著的结果是，对于低水平的基线趋化反应性，趋化反应性的给定相对降低会导致目标清除率的严重不足，而对于高水平的基线反应性则不然。然后将一般模型结果应用于肺泡巨噬细胞从肺表面清除细菌的具体例子。结果表明，与体外测量值相似的适度水平的巨噬细胞趋化反应性，可以解释在典型细菌比生长速率和肺泡巨噬细胞数量密度值下，实验观察到的从肺中清除细菌的速率。
