Assessing mucociliary transport of single particles in vivo shows variable speed and preference for the ventral trachea in newborn pigs.
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.
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.
Mark J
MJ
Hoegger
Maged
M
Awadalla
Eman
E
Namati
Omar A
OA
Itani
Anthony J
AJ
Fischer
Alexander J
AJ
Tucker
Ryan J
RJ
Adam
Geoffrey
G
McLennan
Eric A
EA
Hoffman
David A
DA
Stoltz
Michael J
MJ
Welsh
D000818:Animals; D000831:Animals, Newborn; D009079:Mucociliary Clearance / Q000502:physiology*; D013552:Swine; D014132:Trachea / Q000502:physiology*