Journal article
Assessing mucociliary transport of single particles in vivo shows variable speed and preference for the ventral trachea in newborn pigs
Proceedings of the National Academy of Sciences - PNAS, Vol.111(6), pp.2355-2360
02/11/2014
DOI: 10.1073/pnas.1323633111
PMCID: PMC3926068
PMID: 24474805
Abstract
Mucociliary transport (MCT) defends lungs by removing particulates, and defective MCT is hypothesized to contribute to the onset of lung diseases such as asthma, chronic bronchitis, and cystic fibrosis. However, testing those hypotheses has been limited by current MCT assays and mouse models of human disease. We developed an in vivo MCT assay in newborn pigs, which share physiological and anatomical features with humans. The X-ray–computed tomographic-based method provided high spatial and temporal resolution. We discovered that particles preferentially travel up the ventral airway surface. We also discovered substantial heterogeneity in rates of individual particle movement, indicating that MCT does not likely involve homogeneous mucus blankets. The granularity of the data may aid understanding of MCT and disease pathogenesis.
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.
Details
- Title: Subtitle
- Assessing mucociliary transport of single particles in vivo shows variable speed and preference for the ventral trachea in newborn pigs
- Creators
- Mark J Hoegger - Departments ofMaged Awadalla - Internal MedicineEman Namati - Internal MedicineOmar A Itani - Internal MedicineAnthony J Fischer - PediatricsAlexander J Tucker - Internal MedicineRyan J Adam - Internal MedicineGeoffrey McLennan - Internal MedicineEric A Hoffman - Radiology, andDavid A Stoltz - Departments ofMichael J Welsh - Departments of
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.111(6), pp.2355-2360
- DOI
- 10.1073/pnas.1323633111
- PMID
- 24474805
- PMCID
- PMC3926068
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Alternative title
- Mucociliary transport in newborn pigs
- Language
- English
- Date published
- 02/11/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pulmonary Medicine; Stead Family Department of Pediatrics; Neurosurgery; Internal Medicine
- Record Identifier
- 9984013202102771
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