| Literature DB >> 24474805 |
Mark J Hoegger1, Maged Awadalla, Eman Namati, Omar A Itani, Anthony J Fischer, Alexander J Tucker, Ryan J Adam, Geoffrey McLennan, Eric A Hoffman, David A Stoltz, Michael J Welsh.
Abstract
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.Entities:
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Year: 2014 PMID: 24474805 PMCID: PMC3926068 DOI: 10.1073/pnas.1323633111
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN: 0027-8424 Impact factor: 11.205