Departments of Molecular Physiology and Biophysics, Internal Medicine, Pediatrics, Radiology, and Biomedical Engineering, and Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242.
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2355-60. doi: 10.1073/pnas.1323633111. Epub 2014 Jan 28.
Mucociliary transport (MCT) is an innate defense mechanism that removes particulates, noxious material, and microorganisms from the lung. Several airway diseases exhibit abnormal MCT, including asthma, chronic bronchitis, and cystic fibrosis. However, it remains uncertain whether MCT abnormalities contribute to the genesis of disease or whether they are secondary manifestations that may fuel disease progression. Limitations of current MCT assays and of current animal models of human disease have hindered progress in addressing these questions. Therefore, we developed an in vivo assay of MCT, and here we describe its use in newborn wild-type pigs. We studied pigs because they share many physiological, biochemical, and anatomical features with humans and can model several human diseases. We used X-ray multidetector-row-computed tomography to track movement of individual particles in the large airways of newborn pigs. Multidetector-row-computed tomography imaging provided high spatial and temporal resolution and registration of particle position to airway anatomy. We discovered that cilia orientation directs particles to the ventral tracheal surface. We also observed substantial heterogeneity in the rate of individual particle movement, and we speculate that variations in mucus properties may be responsible. The increased granularity of MCT data provided by this assay may provide an opportunity to better understand host defense mechanisms and the pathogenesis of airway disease.
黏液纤毛传输(Mucociliary Transport,MCT)是一种先天防御机制,可将颗粒物、有害物质和微生物从肺部清除。几种气道疾病表现出异常的 MCT,包括哮喘、慢性支气管炎和囊性纤维化。然而,目前尚不清楚 MCT 异常是否是疾病发生的原因,或者它们是否是可能推动疾病进展的继发性表现。当前 MCT 检测方法和人类疾病的现有动物模型的局限性阻碍了对这些问题的研究进展。因此,我们开发了一种体内 MCT 检测方法,并在此描述了其在新生野生型猪中的应用。我们选择研究猪,是因为它们在生理、生化和解剖学方面与人类有许多相似之处,并且可以模拟几种人类疾病。我们使用 X 射线多排探测器计算机断层扫描(Multidetector-row-computed Tomography,MDCT)来追踪新生猪大气道中单个颗粒的运动。MDCT 成像提供了高空间和时间分辨率,并将颗粒位置与气道解剖结构进行了注册。我们发现纤毛的方向将颗粒导向气管的腹侧表面。我们还观察到单个颗粒运动速度存在显著的异质性,我们推测这可能与黏液性质的变化有关。该检测方法提供的 MCT 数据增加了粒度,这可能为更好地理解宿主防御机制和气道疾病的发病机制提供了机会。