Abstract
Airway surface liquid is comprised of mucus and an underlying, watery periciliary liquid (PCL). In contrast to the well-described axial transport of mucus along airway surfaces via ciliary action, theoretical analyses predict that the PCL is nearly stationary. Conventional and confocal microscopy of fluorescent microspheres and photoactivated fluorescent dyes were used with well-differentiated human tracheobronchial epithelial cell cultures exhibiting spontaneous, radial mucociliary transport to study the movements of mucus and PCL. These studies showed that the entire PCL is transported at approximately the same rate as mucus, 39.2+/-4.7 and 39.8+/-4.2 micrometer/sec, respectively. Removing the mucus layer reduced PCL transport by > 80%, to 4.8+/-0.6 micrometer/sec, a value close to that predicted from theoretical analyses of the ciliary beat cycle. Hence, the rapid movement of PCL is dependent upon the transport of mucus. Mucus-dependent PCL transport was spatially uniform and exceeded the rate expected for pure frictional coupling with the overlying mucus layer; hence, ciliary mixing most likely accelerates the diffusion of momentum from mucus into the PCL. The cephalad movement of PCL along airway epithelial surfaces makes this mucus-driven transport an important component of salt and water physiology in the lung in health and disease.
Full Text
The Full Text of this article is available as a PDF (2.8 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blake J. R., Sleigh M. A. Mechanics of ciliary locomotion. Biol Rev Camb Philos Soc. 1974 Feb;49(1):85–125. doi: 10.1111/j.1469-185x.1974.tb01299.x. [DOI] [PubMed] [Google Scholar]
- Boucher R. C. Human airway ion transport. Part one. Am J Respir Crit Care Med. 1994 Jul;150(1):271–281. doi: 10.1164/ajrccm.150.1.8025763. [DOI] [PubMed] [Google Scholar]
- Boucher R. C. Human airway ion transport. Part two. Am J Respir Crit Care Med. 1994 Aug;150(2):581–593. doi: 10.1164/ajrccm.150.2.8049852. [DOI] [PubMed] [Google Scholar]
- Eliezer N., Sadé J., Silberberg A., Nevo A. C. The role of mucus in transport by cilia. Am Rev Respir Dis. 1970 Jul;102(1):48–52. doi: 10.1164/arrd.1970.102.1.48. [DOI] [PubMed] [Google Scholar]
- Folkesson H. G., Matthay M. A., Frigeri A., Verkman A. S. Transepithelial water permeability in microperfused distal airways. Evidence for channel-mediated water transport. J Clin Invest. 1996 Feb 1;97(3):664–671. doi: 10.1172/JCI118463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Folkesson H. G., Matthay M. A., Hasegawa H., Kheradmand F., Verkman A. S. Transcellular water transport in lung alveolar epithelium through mercury-sensitive water channels. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4970–4974. doi: 10.1073/pnas.91.11.4970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fulford G. R., Blake J. R. Muco-ciliary transport in the lung. J Theor Biol. 1986 Aug 21;121(4):381–402. doi: 10.1016/s0022-5193(86)80098-4. [DOI] [PubMed] [Google Scholar]
- Gatto L. A. Cholinergic and adrenergic stimulation of mucociliary transport in the rat trachea. Respir Physiol. 1993 May;92(2):209–217. doi: 10.1016/0034-5687(93)90039-d. [DOI] [PubMed] [Google Scholar]
- Gray T. E., Guzman K., Davis C. W., Abdullah L. H., Nettesheim P. Mucociliary differentiation of serially passaged normal human tracheobronchial epithelial cells. Am J Respir Cell Mol Biol. 1996 Jan;14(1):104–112. doi: 10.1165/ajrcmb.14.1.8534481. [DOI] [PubMed] [Google Scholar]
- Jiang C., Finkbeiner W. E., Widdicombe J. H., McCray P. B., Jr, Miller S. S. Altered fluid transport across airway epithelium in cystic fibrosis. Science. 1993 Oct 15;262(5132):424–427. doi: 10.1126/science.8211164. [DOI] [PubMed] [Google Scholar]
- Kaartinen L., Nettesheim P., Adler K. B., Randell S. H. Rat tracheal epithelial cell differentiation in vitro. In Vitro Cell Dev Biol Anim. 1993 Jun;29A(6):481–492. [PubMed] [Google Scholar]
- Kilburn K. H. A hypothesis for pulmonary clearance and its implications. Am Rev Respir Dis. 1968 Sep;98(3):449–463. doi: 10.1164/arrd.1968.98.3.449. [DOI] [PubMed] [Google Scholar]
- King M., Agarwal M., Shukla J. B. A planar model for mucociliary transport: effect of mucus viscoelasticity. Biorheology. 1993 Jan-Feb;30(1):49–61. [PubMed] [Google Scholar]
- Mercer R. R., Russell M. L., Roggli V. L., Crapo J. D. Cell number and distribution in human and rat airways. Am J Respir Cell Mol Biol. 1994 Jun;10(6):613–624. doi: 10.1165/ajrcmb.10.6.8003339. [DOI] [PubMed] [Google Scholar]
- Quinton P. M. Viscosity versus composition in airway pathology. Am J Respir Crit Care Med. 1994 Jan;149(1):6–7. doi: 10.1164/ajrccm.149.1.8111599. [DOI] [PubMed] [Google Scholar]
- Rahmoune H., Shephard K. L. State of airway surface liquid on guinea pig trachea. J Appl Physiol (1985) 1995 Jun;78(6):2020–2024. doi: 10.1152/jappl.1995.78.6.2020. [DOI] [PubMed] [Google Scholar]
- Sanderson M. J., Sleigh M. A. Ciliary activity of cultured rabbit tracheal epithelium: beat pattern and metachrony. J Cell Sci. 1981 Feb;47:331–347. doi: 10.1242/jcs.47.1.331. [DOI] [PubMed] [Google Scholar]
- Satir P., Sleigh M. A. The physiology of cilia and mucociliary interactions. Annu Rev Physiol. 1990;52:137–155. doi: 10.1146/annurev.ph.52.030190.001033. [DOI] [PubMed] [Google Scholar]
- Serafini S. M., Michaelson E. D. Length and distribution of cilia in human and canine airways. Bull Eur Physiopathol Respir. 1977 Jul-Aug;13(4):551–559. [PubMed] [Google Scholar]
- Shah P. L., Scott S. F., Knight R. A., Marriott C., Ranasinha C., Hodson M. E. In vivo effects of recombinant human DNase I on sputum in patients with cystic fibrosis. Thorax. 1996 Feb;51(2):119–125. doi: 10.1136/thx.51.2.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith J. J., Travis S. M., Greenberg E. P., Welsh M. J. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell. 1996 Apr 19;85(2):229–236. doi: 10.1016/s0092-8674(00)81099-5. [DOI] [PubMed] [Google Scholar]
- TOREMALM N. G. The daily amoung of tracheo-bronchial secretions in man. A method for continuous tracheal aspiration in laryngectomized and tracheotomized patients. Acta Otolaryngol Suppl. 1960;158:43–53. doi: 10.3109/00016486009122392. [DOI] [PubMed] [Google Scholar]
- Vasconcellos C. A., Allen P. G., Wohl M. E., Drazen J. M., Janmey P. A., Stossel T. P. Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolin. Science. 1994 Feb 18;263(5149):969–971. doi: 10.1126/science.8310295. [DOI] [PubMed] [Google Scholar]
- Wills P. J., Garcia Suarez M. J., Rutman A., Wilson R., Cole P. J. The ciliary transportability of sputum is slow on the mucus-depleted bovine trachea. Am J Respir Crit Care Med. 1995 Apr;151(4):1255–1258. doi: 10.1164/ajrccm.151.4.7697262. [DOI] [PubMed] [Google Scholar]
- Wu R., Yankaskas J., Cheng E., Knowles M. R., Boucher R. Growth and differentiation of human nasal epithelial cells in culture. Serum-free, hormone-supplemented medium and proteoglycan synthesis. Am Rev Respir Dis. 1985 Aug;132(2):311–320. doi: 10.1164/arrd.1985.132.2.311. [DOI] [PubMed] [Google Scholar]
- Yeates D. B., Aspin N., Levison H., Jones M. T., Bryan A. C. Mucociliary tracheal transport rates in man. J Appl Physiol. 1975 Sep;39(3):487–495. doi: 10.1152/jappl.1975.39.3.487. [DOI] [PubMed] [Google Scholar]
- Yguerabide J., Schmidt J. A., Yguerabide E. E. Lateral mobility in membranes as detected by fluorescence recovery after photobleaching. Biophys J. 1982 Oct;40(1):69–75. doi: 10.1016/S0006-3495(82)84459-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoneda K. Mucous blanket of rat bronchus: an ultrastructural study. Am Rev Respir Dis. 1976 Nov;114(5):837–842. doi: 10.1164/arrd.1976.114.5.837. [DOI] [PubMed] [Google Scholar]