Regional Differences in Mucociliary Clearance in the Upper and Lower Airways

Abstract

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 ∼3–4× greater than on the tracheal wall. This appeared to be due to a more abundant population of ciliated cells in the nasal cavity (∼80%) compared to the more sparsely ciliated trachea (∼40%). 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 (Bpifb1 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 ∼10-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.

Neutralisation of SARS-CoV-2 by monoclonal antibody through dual targeting powder formulation

“…In addition, neutralising mAb must be present at the airway epithelium to interfere with the virus-host interaction before viral entry occurs. The rate of mucociliary clearance in the nasal cavity is higher than that in the lower airways due to the higher population of ciliated cells [ 41 ]. As a result, particles deposited in the nasal cavity tend to be removed more quickly from the airways.…”

Prolonged airway explant culture enables study of health, disease, and viral pathogenesis

“…Mucociliary clearance . To measure mucociliary clearance, fluorescently labeled beads (200 nm) were aerosolized onto the surface of airway tissue explants, visualized under a dissecting microscope, and recorded, as previously 22 .…”

CFTR dysfunction leads to defective bacterial eradication on cystic fibrosis airways

“…First, the mucociliary clearance mechanism is constructed by viscoelastic and discontinued mucus ( Rogers et al, 2022 ; Abrami et al, 2024 ) that flow on a watery and gel-like layer, the periciliary layer (PCL) ( Widdicombe and Widdicombe, 1995 ; Button et al, 2012 ) ( Figure 1 ). Sticky mucus traps inhaled bacteria, debris and other particles, while the cilia of epithelial cells in the underlying PCL propel the mucus and trapped substances ( Figure 1 ) towards to the pharynx, where they form the sputum for expectoration ( Bustamante-Marin and Ostrowski, 2017 ; Rogers et al, 2022 ).…”