Assessing mucociliary transport of single particles in vivo shows variable speed and preference for the ventral trachea in newborn pigs

Mark Hoegger, Maged Awadalla, Eman Namati, Omar Itani, Anthony Fischer, Alexander Tucker, Ryan Adam, Geoffrey McLennan, Eric Hoffman, David Stoltz, Michael Welsh

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2355-2360
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number6
DOIs
Publication statusPublished - 2014

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