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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cellular Biology and Physiology Subcommittee 1 (CBY)
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University of Washington
Schools of Medicine
United States
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Verdugo, P; Golborne, C E (1988) Remote detection of ciliary movement by fiber optic laser-Doppler spectroscopy. IEEE Trans Biomed Eng 35:303-7
Verdugo, P; Deyrup-Olsen, I; Aitken, M et al. (1987) Molecular mechanism of mucin secretion: I. The role of intragranular charge shielding. J Dent Res 66:506-8