Rogers Troy D, Button Brian, Kelada Samir N P, Ostrowski Lawrence E, Livraghi-Butrico Alessandra, Gutay Mark I, Esther Charles R, Grubb Barbara R
Marsico Lung Institute, University of North Carolina School of Medicine, Chapel Hill, NC, United States.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Front Physiol. 2022 Mar 9;13:842592. doi: 10.3389/fphys.2022.842592. eCollection 2022.
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 ( 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.
由于鼻腔是哺乳动物吸入空气的入口，该区域暴露于吸入颗粒物和病原体的最高浓度环境中，必须清除这些物质以保持下呼吸道无菌。因此，人们可能期望通过该区域的黏液纤毛清除（MCC）有力地清除这些物质。我们研究了小鼠鼻腔与更远端气道（气管）相比的MCC速率。鼻腔（鼻咽后部，PNP）的MCC速率比气管壁上的速率大约高3 - 4倍。这似乎是由于鼻腔中纤毛细胞的数量比纤毛较少的气管（约40%）更为丰富（约80%）。有趣的是，气管腹侧壁的MCC速率明显低于气管后膜。后膜上纤毛上皮下方的气管肌似乎控制着表面结构，并且可能部分控制了该气管区域的MCC速率。在我们的一个小鼠模型（KO）中，灌洗液中MUC5B蛋白增加了3倍，气管壁上的MCC颗粒运输严重受损，但气管后膜上的MCC正常发生。虽然黏液层覆盖了PNP和气管的表面，但这种黏液似乎仅在PNP中通过MCC作为一个整体被运输。相比之下，颗粒在气管中似乎以离散的斑块或黏液流的形式被运输。此外，PNP中的颗粒运输相当线性，而气管中颗粒的运输通常遵循更非线性的路径。覆盖PNP的厚而黏弹性黏液层，其黏液质量比覆盖气管表面的黏液层大10倍左右，可以在完全没有细胞的大面积区域（由上皮层破裂形成）上被运输。相比之下，颗粒甚至无法在气管上皮的小破裂处被运输。PNP中的厚黏液层可能有助于颗粒在鼻腔中非纤毛嗅觉细胞上的运输，并且可能有助于该上呼吸道区域的加湿和更有效地捕获颗粒。
