Cystic Fibrosis Research and Treatment Center, University of North Carolina, Chapel Hill, NC 27599-7248, USA.
Science. 2012 Aug 24;337(6097):937-41. doi: 10.1126/science.1223012.
Mucus clearance is the primary defense mechanism that protects airways from inhaled infectious and toxic agents. In the current 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 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.
黏液清除是保护气道免受吸入性感染和有毒物质侵害的主要防御机制。在当前的凝胶-液相黏液清除模型中,黏液凝胶被推动到围绕纤毛的“水相”纤毛层之上。然而,该模型无法解释健康状态下黏液层的形成,也无法解释为什么在疾病状态下黏液清除会失败。我们提出了一种凝胶-毛刷模型,其中纤毛层被跨膜黏蛋白和与气道表面紧密结合的黏多糖所占据。这种毛刷阻止了黏液渗透到纤毛间隙,并使黏液形成一个明显的层。黏液和纤毛毛刷层的相对渗透压解释了健康状态下黏液清除的稳定性及其在气道疾病中的失败原因。