{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:09:22Z","timestamp":1790204962510,"version":"4.1.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["GRUBB17XX0"],"award-info":[{"award-number":["GRUBB17XX0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["BUTTON19G0"],"award-info":[{"award-number":["BUTTON19G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL125280"],"award-info":[{"award-number":["R01 HL125280"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL13691"],"award-info":[{"award-number":["R01 HL13691"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P01 HL10880"],"award-info":[{"award-number":["P01 HL10880"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>As the nasal cavity is the portal of entry for inspired air in mammals, this region is exposed to the highest concentration of inhaled particulate matter and pathogens, which must be removed to keep the lower airways sterile. Thus, one might expect vigorous removal of these substances via mucociliary clearance (MCC) in this region. We have investigated the rate of MCC in the murine nasal cavity compared to the more distal airways (trachea). The rate of MCC in the nasal cavity (posterior nasopharynx, PNP) was \u223c3\u20134\u00d7 greater than on the tracheal wall. This appeared to be due to a more abundant population of ciliated cells in the nasal cavity (\u223c80%) compared to the more sparsely ciliated trachea (\u223c40%). Interestingly, the tracheal ventral wall exhibited a significantly lower rate of MCC than the tracheal posterior membrane. The trachealis muscle underlying the ciliated epithelium on the posterior membrane appeared to control the surface architecture and likely in part the rate of MCC in this tracheal region. In one of our mouse models (<jats:italic>Bpifb1<\/jats:italic> KO) exhibiting a 3-fold increase in MUC5B protein in lavage fluid, MCC particle transport on the tracheal walls was severely compromised, yet normal MCC occurred on the tracheal posterior membrane. While a blanket of mucus covered the surface of both the PNP and trachea, this mucus appeared to be transported as a blanket by MCC only in the PNP. In contrast, particles appeared to be transported as discrete patches or streams of mucus in the trachea. In addition, particle transport in the PNP was fairly linear, in contrast transport of particles in the trachea often followed a more non-linear route. The thick, viscoelastic mucus blanket that covered the PNP, which exhibited \u223c10-fold greater mass of mucus than did the blanket covering the surface of the trachea, could be transported over large areas completely devoid of cells (made by a breach in the epithelial layer). In contrast, particles could not be transported over even a small epithelial breach in the trachea. The thick mucus blanket in the PNP likely aids in particle transport over the non-ciliated olfactory cells in the nasal cavity and likely contributes to humidification and more efficient particle trapping in this upper airway region.<\/jats:p>","DOI":"10.3389\/fphys.2022.842592","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T11:23:17Z","timestamp":1646824997000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Regional Differences in Mucociliary Clearance in the Upper and Lower Airways"],"prefix":"10.3389","volume":"13","author":[{"given":"Troy D.","family":"Rogers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Button","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir N. P.","family":"Kelada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence E.","family":"Ostrowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Livraghi-Butrico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark I.","family":"Gutay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Charles R.","family":"Esther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara R.","family":"Grubb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1164\/arrd.1970.102.3.388","article-title":"Mucociliary clearance rates at various levels in dog lungs.","volume":"102","author":"Asmundsson","year":"1970","journal-title":"Am. Rev. Respir. Dis."},{"key":"B2","first-page":"2649","article-title":"Cystic fibrosis","author":"Boat","year":"1989","journal-title":"The Metabolic Basis of Inherited Disease"},{"key":"B3","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1056\/NEJMra1813799","article-title":"Muco-obstructive lung diseases.","volume":"380","author":"Boucher","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1177\/000348947007900315","article-title":"The uptake of inhaled gases by the nose.","volume":"79","author":"Brain","year":"1970","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3109\/01902148709064317","article-title":"Tracheal mucociliary transport in laboratory mice: evidence for genetic polymorphism.","volume":"13","author":"Brownstein","year":"1987","journal-title":"Exp. Lung Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1126\/science.1223012","article-title":"A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia.","volume":"337","author":"Button","year":"2012","journal-title":"Science"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1016\/j.jbiomech.2016.04.009","article-title":"A parametric study of mucociliary transport by numerical simulations of 3D non-homogeneous mucus.","volume":"49","author":"Chatelin","year":"2016","journal-title":"J. Biomech."},{"key":"B8","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1165\/rcmb.2017-0127OC","article-title":"Role of spdef in the regulation of Muc5b expression in the airways of naive and mucoobstructed mice.","volume":"59","author":"Chen","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0034-5687(72)90086-2","article-title":"Squeegee of fluid in the compressed canine trachea.","volume":"16","author":"Coburn","year":"1972","journal-title":"Respir. Physiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1146\/annurev.physiol.70.113006.100638","article-title":"Regulated airway goblet cell mucin secretion.","volume":"70","author":"Davis","year":"2008","journal-title":"Annu. Rev. Physiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1097\/00063198-200311000-00007","article-title":"Update on pathogenesis of cystic fibrosis lung disease.","volume":"9","author":"Donaldson","year":"2003","journal-title":"Curr. Opin. Pulm. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3689","DOI":"10.1038\/srep03689","article-title":"Non-invasive airway health assessment: synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo.","volume":"4","author":"Donnelley","year":"2014","journal-title":"Sci. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1534\/genetics.117.300211","article-title":"Identification of trans Protein QTL for secreted airway mucins in mice and a causal role for Bpifb1.","volume":"207","author":"Donoghue","year":"2017","journal-title":"Genetics"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1101\/2020.06.17.155846","article-title":"BPIFB1 loss alters airway mucus properties and diminishes mucociliary clearance.","author":"Donoghue","year":"2020","journal-title":"BioRxiv"},{"key":"B15","doi-asserted-by":"publisher","first-page":"145","DOI":"10.15326\/jcopdf.6.2.2018.0156","article-title":"The clinical features of bronchiectasis associated with Alpha-1 antitrypsin deficiency, common variable immunodeficiency and primary ciliary dyskinesia\u2013results from the U.S. Bronchiectasis research registry.","volume":"6","author":"Eden","year":"2019","journal-title":"Chronic. Obstr. Pulm. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"16528","DOI":"10.1073\/pnas.1206552109","article-title":"Overexpressing mouse model demonstrates the protective role of Muc5ac in the lungs.","volume":"109","author":"Ehre","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B17","doi-asserted-by":"publisher","first-page":"L398","DOI":"10.1152\/ajplung.00398.2016","article-title":"Sialic acid-to-urea ratio as a measure of airway surface hydration.","volume":"312","author":"Esther","year":"2017","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1165\/rcmb.2004-0060OC","article-title":"Mucin is produced by clara cells in the proximal airways of antigen-challenged mice.","volume":"31","author":"Evans","year":"2004","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B19","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1056\/NEJMra0910061","article-title":"Airway mucus function and dysfunction.","volume":"363","author":"Fahy","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"L1270","DOI":"10.1152\/ajplung.00485.2019","article-title":"Normal murine respiratory tract has its mucus concentrated in clouds based on the Muc5b mucin.","volume":"318","author":"Fakih","year":"2020","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1093\/infdis\/135.1.9","article-title":"Differential distribution of ciliated epithelial cells in the trachea of hamsters: implications for studies of pathogenesis.","volume":"135","author":"Gabridge","year":"1977","journal-title":"J. Infect. Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"L860","DOI":"10.1152\/ajplung.00015.2016","article-title":"Reduced mucociliary clearance in old mice is associated with a decrease in Muc5b mucin.","volume":"310","author":"Grubb","year":"2016","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"C615","DOI":"10.1152\/ajpcell.2001.281.2.C615","article-title":"Alterations in airway ion transport in NKCC1-deficient mice.","volume":"281","author":"Grubb","year":"2001","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"C293","DOI":"10.1152\/ajpcell.1994.267.1.C293","article-title":"Anomalies in ion transport in CF mouse tracheal epithelium.","volume":"267","author":"Grubb","year":"1994","journal-title":"Am. J. Physiol."},{"key":"B25","doi-asserted-by":"crossref","first-page":"C574","DOI":"10.1152\/ajpcell.00106.2007","article-title":"Olfactory epithelia exhibit progressive functional and morphological defects in CF mice.","volume":"293","author":"Grubb","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"5363","DOI":"10.1038\/s41467-018-07768-9","article-title":"Muc5b overexpression causes mucociliary dysfunction and enhances lung fibrosis in mice.","volume":"9","author":"Hancock","year":"2018","journal-title":"Nat. Commun."},{"key":"B27","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1002\/path.1711060204","article-title":"Mucus transport in the tracheobronchial tree of normal and bronchitic rats.","volume":"106","author":"Iravani","year":"1972","journal-title":"J. Pathol."},{"key":"B28","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1159\/000193659","article-title":"Mucociliary activity in the respiratory tract as influenced by prostaglandin E1.","volume":"32","author":"Iravani","year":"1975","journal-title":"Respiration"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e0199319","DOI":"10.1371\/journal.pone.0199319","article-title":"New insights into the mechanisms controlling the bronchial mucus balance.","volume":"13","author":"Karamaoun","year":"2018","journal-title":"PLoS One"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1007\/s10439-016-1743-y","article-title":"Effect of fluid viscosity on the cilia-generated flow on a mouse tracheal lumen.","volume":"45","author":"Kikuchi","year":"2017","journal-title":"Ann. Biomed. Eng."},{"key":"B31","doi-asserted-by":"publisher","first-page":"L144","DOI":"10.1152\/ajplung.00117.2013","article-title":"Fluctuation of cilia-generated flow on the surface of the tracheal lumen.","volume":"306","author":"Kiyota","year":"2014","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1183\/09031936.00015108","article-title":"Muscarinic receptor subtypes in cilia-driven transport and airway epithelial development.","volume":"33","author":"Klein","year":"2009","journal-title":"Eur. Respir. J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"eaav3505","DOI":"10.1126\/scitranslmed.aav3505","article-title":"Intranasal micro-optical coherence tomography imaging for cystic fibrosis studies.","volume":"11","author":"Leung","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"B34","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1001\/archotol.1934.03600040074006","article-title":"Principles underlying ciliary activity in the respiratory tract.","volume":"20","author":"Lucus","year":"1934","journal-title":"Arch. Otolaryngol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1164\/rccm.201910-1943SO","article-title":"Cystic fibrosis: emergence of highly effective targeted therapeutics and potential clinical implications.","volume":"201","author":"Mall","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B36","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/ar.1090071102","article-title":"The trachealis muscle. Its arrangement at the carina tracheae and its probable influence on the lodgment of foreign bodies in the right bronchus and lung.","volume":"7","author":"Miller","year":"1913","journal-title":"Anat. Rec."},{"key":"B37","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1164\/arrd.1984.130.2.275","article-title":"The nasal mucociliary apparatus. Correlation of structure and function in the rat.","volume":"130","author":"Morgan","year":"1984","journal-title":"Am. Rev. Respir. Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1164\/rccm.201804-0734OC","article-title":"Localization of secretory mucins MUC5AC and MUC5B in normal\/healthy human airways.","volume":"199","author":"Okuda","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1165\/rcmb.2009-0118OC","article-title":"Conditional deletion of dnaic1 in a murine model of primary ciliary dyskinesia causes chronic rhinosinusitis.","volume":"43","author":"Ostrowski","year":"2010","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/BF00234174","article-title":"The distribution and structure of cells in the tracheal epithelium of the mouse.","volume":"208","author":"Pack","year":"1980","journal-title":"Cell Tissue Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"14875","DOI":"10.1074\/jbc.C109.000869","article-title":"Transmembrane protein 16A (TMEM16A) is a Ca2 +-regulated Cl- secretory channel in mouse airways.","volume":"284","author":"Rock","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"14744","DOI":"10.1038\/s41598-018-33053-2","article-title":"Mucociliary clearance in mice measured by tracking trans-tracheal fluorescence of nasally aerosolized beads.","volume":"8","author":"Rogers","year":"2018","journal-title":"Sci. Rep."},{"key":"B43","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1056\/NEJMra043184","article-title":"Cystic fibrosis.","volume":"352","author":"Rowe","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/nature12807","article-title":"Muc5b is required for airway defence.","volume":"505","author":"Roy","year":"2014","journal-title":"Nature"},{"key":"B45","doi-asserted-by":"publisher","first-page":"L99","DOI":"10.1152\/ajplung.00024.2015","article-title":"Continuous mucociliary transport by primary human airway epithelial cells in vitro.","volume":"309","author":"Sears","year":"2015","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"L1036","DOI":"10.1152\/ajplung.1997.273.5.L1036","article-title":"Heterogeneity of the composition and thickness of tracheal mucus in rats.","volume":"273","author":"Sims","year":"1997","journal-title":"Am. J. Physiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1046\/j.1365-2818.2003.01209.x","article-title":"All-digital image capture and whole-field analysis of ciliary beat frequency.","volume":"211","author":"Sisson","year":"2003","journal-title":"J. Microsc."},{"key":"B48","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.resp.2008.03.006","article-title":"Modelling mucociliary clearance.","volume":"163","author":"Smith","year":"2008","journal-title":"Respir. Physiol. Neurobiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/0034-5687(76)90049-9","article-title":"Mechanical activities of trachea as measured in vitro and in vivo.","volume":"26","author":"Souhrada","year":"1976","journal-title":"Respir. Physiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1164\/arrd.1977.115.5.819","article-title":"The mucous lining of major bronchi in the rabbit lung.","volume":"115","author":"Sturgess","year":"1977","journal-title":"Am. Rev. Respir. Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/s41598-017-00769-6","article-title":"Intubation-free in vivo imaging of the tracheal mucosa using two-photon microscopy.","volume":"7","author":"Veres","year":"2017","journal-title":"Sci. Rep."},{"key":"B52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.1963.43.1.1","article-title":"Regulation of tracheobronchial smooth muscle.","volume":"43","author":"Widdicombe","year":"1963","journal-title":"Physiol. Rev."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1097\/00003246-199611000-00025","article-title":"Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa.","volume":"24","author":"Williams","year":"1996","journal-title":"Crit. Care Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.3934\/mbe.2015.12.1107","article-title":"Cilium height difference between strokes is more effective in driving fluid transport in mucociliary clearance: a numerical study.","volume":"12","author":"Xu","year":"2015","journal-title":"Math. Biosci. Eng."},{"key":"B55","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1165\/rcmb.2017-0387OC","article-title":"Mice with a deletion of rsph1 exhibit a low level of mucociliary clearance and develop a primary ciliary dyskinesia phenotype.","volume":"61","author":"Yin","year":"2019","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1165\/rcmb.2005-0460OC","article-title":"Central role of Muc5ac expression in mucous metaplasia and its regulation by conserved 5\u2019 elements.","volume":"37","author":"Young","year":"2007","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1113\/jphysiol.2007.149310","article-title":"Munc13-2-\/-baseline secretion defect reveals source of oligomeric mucins in mouse airways.","volume":"586","author":"Zhu","year":"2008","journal-title":"J. Physiol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.842592\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T11:23:38Z","timestamp":1646825018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.842592\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,9]]},"references-count":57,"alternative-id":["10.3389\/fphys.2022.842592"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.842592","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,9]]},"article-number":"842592"}}