CELL PHYSIOLOGY OF CILIARY MOVEMENT IN THE LUNG

排列在气道粘膜上的纤毛细胞是呼吸道的发动机。 输送带系统，其中粘液用作流体输送器。 由该系统驱动的粘膜纤毛清除是关键的 在防御肺部感染和吸入的组成部分 污染物 虽然粘膜纤毛清除是一种功能， 在气道的慢性炎症过程中受损最严重， 对如何监管的理解仍然非常不确定。 的 生理机制的知识，调节两个运动， 呼吸道纤毛和呼吸道粘液的流变学特性是一种 研究粘液纤毛控制的必要前提 间隙 我们的实验室一直在研究控制纤毛虫 细胞和粘液流变学多年来，并取得了一些新的 对这个领域的贡献。 我们开发了一种新的激光多普勒方法， 精确检测纤毛运动，以及研究激素或其他 递质控制哺乳动物纤毛细胞中的纤毛运动（Lee和 Verdugo，Biophys. J.，1976; Verdugo等人，应用生理学杂志，1980年; Verdugo，Nature，1980）。 我们证明了粘液的流变特性 由类似于唐南平衡（Tam 和Verdugo，自然，1981年），最关键的理解， 粘液流变学的调节，提供了宝贵的新见解， 囊性纤维化的病理生理学 该计划支持的研究 将致力于扩展细胞机制的研究 调节纤毛运动，识别细胞外信息， 能够激活呼吸纤毛的运动， 细胞接受的激素或其他化学递质的刺激 膜被中继到纤毛轴丝的收缩装置。 我们计划进一步探索机制，使呼吸纤毛 当粘性负荷增加时，细胞自动调节。 系统 开发新的治疗策略， 航空公司在很大程度上依赖于对基本机制的理解， 控制纤毛清除粘液纤毛。 这里提出的研究将 增加我们对肺纤毛运动控制的理解 并将为生理学的细胞基础提供新的见解， 气道中粘液纤毛运输的药理学和病理生理学。

The ciliated cells that line the mucosa of the airways are the engine of conveyor belt system where mucus functions as a fluidic conveyor. Mucociliary clearance which is driven by this system is a critical component in the defense of the lung against infection and inhaled pollutants. Although mucociliary clearance is one of the functions which is most impaired in chronic inflammatory process of the airways, the understanding of how it is regulated is still very uncertain. The knowledge of the physiologic mechanisms that regulate both the movements of respiratory cilia and the rheological properties of respiratory mucus is a necessary prerequisite in the investigation of the control of mucociliary clearance. Our laboratory has been investigating the control of ciliated cells and mucus rheology for several years and has made a number of novel contributions to this field. We developed a new laser-Doppler method to precisely detect ciliary movement, and the study of how hormones or other transmitters control ciliary movements in mammalian ciliated cells (Lee and Verdugo, Biophys. J., 1976; Verdugo et al., J. Appl. Physiol., 1980; Verdugo, Nature, 1980). We demonstrated that mucus rheological properties are controlled by a process of hydration similar to Donnan equilibrium (Tam and Verdugo, Nature, 1981), most critical in the understanding of the regulation of mucus rheology that gives invaluable new insights into the pathophysiology of Cystic Fibrosis. Research supported by this program will be dedicated to extending the study of the cellular mechanisms regulating ciliary movements, to identifying the extracellular messages that activate motion in respiratory cilia, and investigating how the stimuli of hormones or other chemical transmitters, received by the cell membrane are relayed to the contractile apparatus of the ciliary axoneme. We plan to further explore the mechanism that allows respiratory ciliated cells to autoregulate when the viscous load is increased. The systematic development of new therapeutic strategies for curing diseases of the airways relies heavily on the understanding of the fundamental mechanism that controls ciliary mucociliary clearance. Research proposed here will increase our understanding of the control of ciliary movements in the lung and will give new insight into the cellular basis of the physiology, pharmacology and pathphysiology of mucociliary transport in the airways.