CELL PHYSIOLOGY OF CILIARY MOVEMENT IN THE LUNG

排列在呼吸道粘膜上的纤毛细胞是 传送带系统，其中粘液起着流体传送器的作用。 由该系统驱动的粘液纤毛清除是一个关键 肺中防御感染和吸入的成分 污染物。虽然粘液纤毛清除是 在慢性呼吸道炎症过程中受损最严重， 对于它是如何被监管的，人们的理解仍然非常不确定。这个 了解调节两种运动的生理机制 呼吸道纤毛和呼吸道粘液的流变性 粘液纤毛控制研究的必要前提 通行证。我们实验室一直在调查纤毛虫的防治 细胞流变学和粘液流变学已有几年的研究成果 对这一领域的贡献。我们开发了一种新的激光多普勒方法来 精确检测纤毛运动，以及研究荷尔蒙或其他 递质控制哺乳动物纤毛细胞的纤毛运动(Lee和 Verdugo，生物物理学。J.，1976；Verdugo等人，J.Appl.PhysIOL.，1980； Verdugo，自然，1980)。我们证明了粘液的流变性 受控于类似于多南平衡的水合过程( 和Verdugo，自然，1981)，在理解 粘液流变学的调节，给了我们宝贵的新见解 囊性纤维化的病理生理学。该计划支持的研究 将致力于扩展对细胞机制的研究 调节纤毛运动，识别细胞外信息 激活呼吸纤毛的运动，并研究 激素或其他化学递质的刺激，由细胞接收 膜被传递到睫状轴突收缩器。 我们计划进一步探索允许呼吸道纤毛的机制 当粘性负荷增加时，细胞自动调节。系统化的 新的治疗策略的发展，以治疗的疾病 航空公司在很大程度上依赖于对基本机制的理解 控制纤毛粘液纤毛清除的物质。这里提出的研究将 加深对肺内纤毛运动控制的了解 并将为生理学的细胞基础提供新的见解， 呼吸道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.