Cystic Fibrosis Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Am J Physiol Lung Cell Mol Physiol. 2011 Aug;301(2):L181-6. doi: 10.1152/ajplung.00321.2010. Epub 2011 Apr 29.
The airway epithelial surface liquid is generally considered to be composed of two layers, a periciliary layer and a continuous thick mucus layer moving in bulk. This view may not be appropriate for all areas of the lung. Our hypothesis, that mucus may form a discontinuous layer with dynamic attachments to the surface, is investigated using a culture system. We used live-cell confocal microscopy to investigate thin mucus layers and fluorescent beads and exogenous MUC5B to visualize mucus dynamics on ciliated human bronchial cultures. A continuous mucus layer was not observed. In sparsely ciliated cultures, mucus attached to ciliated cells; however, in highly ciliated cultures, mucus formed strands several hundred micrometers long. As with increases in ciliation, increases in bead concentration caused the appearance of mucus strands. We confirmed the involvement of mucins in the binding of mucus to cilia by adding labeled purified MUC5B to the cultures. These data suggest that mucins may have an intrinsic ability to form attachments to cilia. The significance of these findings is that aberrant modulation of such an intrinsic property may explain the initiation of highly adherent mucus in cystic fibrosis lung disease.
气道上皮表面液体通常被认为由两层组成,即纤毛层和整体移动的连续厚黏液层。这一观点可能并不适用于肺部的所有区域。我们的假设是,黏液可能与表面形成不连续的层,并具有动态附着,我们使用培养系统对此进行了研究。我们使用活细胞共聚焦显微镜研究了薄黏液层和荧光珠以及外源性 MUC5B 在人支气管纤毛培养物上对黏液动力学的可视化。没有观察到连续的黏液层。在纤毛稀疏的培养物中,黏液附着在纤毛细胞上;然而,在纤毛高度密集的培养物中,黏液形成了数百微米长的链。随着纤毛的增加,珠浓度的增加导致了黏液链的出现。我们通过向培养物中添加标记的纯化 MUC5B 证实了黏蛋白在黏液与纤毛结合中的作用。这些数据表明,黏蛋白可能具有与纤毛形成附着的内在能力。这些发现的意义在于,对这种内在特性的异常调节可能解释了囊性纤维化肺部疾病中高度黏附性黏液的起始。