Mucus clearance is the primary defense mechanism that protects airways from inhaled infectious and toxic agents. In the classical gel-on-liquid mucus clearance model, a mucus gel is propelled on top of a “watery” periciliary layer surrounding the cilia. However, this model fails to explain the formation of a distinct mucus layer in health or why mucus clearance fails in disease. We propose and verified a gel-on-brush model in which the periciliary layer is occupied by membrane-spanning mucins and mucopolysaccharides densely tethered to the airway surface. This brush prevents mucus penetration into the periciliary space and causes mucus to form a distinct layer. The relative osmotic moduli of the mucus and periciliary brush layers explain both the stability of mucus clearance in health and its failure in airway disease. We demonstrated a strong correlation between the extent of the chronic bronchitis disease and the state of hydration of the airway surface layer – mucus concentration and the corresponding osmotic pressure.
We are using these ideas to develop biomarkers and treatment strategies for patients with different airway diseases.
- “A Periciliary Brush Promotes the Lung Health by Separating the Mucus Layer from Airway Epithelia” by B. Button, L. Cai, C. Ehre, M. Kesimer, D. B. Hill, J. K. Sheehan, R. C. Boucher, and M. Rubinstein, Science 337, 937-941 (2012). Highlighted in “Walking on Solid Ground” by B. F. Dickey Science 337, 924 (2012).
- “The Relationship of Mucus Concentration (Hydration) to Mucus Osmotic Pressure and Transport in Chronic Bronchitis” by Wayne H Anderson, Raymond D Coakley, Brian Button, Ashley G Henderson, Kirby L Zeman, Neil E Alexis, David B Peden, Eduardo R Lazarowski, C. William Davis, Summer Bailey, Fred Fuller, Martha Almond, Bahjat Qaqish, Elena Bordonali, Michael Rubinstein, William D Bennett, Mehmet Kesimer, and Richard C Boucher, Am. J Respir. Crit. Care Med. 24 Apr 2015; DOI: 10.1164/rccm.201412-2230OC
- “A Physical Linkage between Cystic Fibrosis Airway Surface Dehydration and Pseudomonas Aeruginosa Biofilms” by I. Matsui, V. E. Wagner, D. B. Hill, U. E. Schwab, T. D. Rogers, B. Button, R. M. Taylor, R. Superfine, M. Rubinstein, B. H. Iglewski, and R. C. Boucher, Proceedings of the National Academy of Sciences of the United States of America, 103, 18131-18136, (2006).