Home LiteratureArticle Details
PMID: 24474805 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Hoegger MJ, Awadalla M, Namati E, Itani OA, Fischer AJ, Tucker AJ, Adam RJ, McLennan G, Hoffman EA, Stoltz DA, Welsh MJ

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.

MeSH Terms
Animals Animals, Newborn Mucociliary Clearance/physiology Swine Trachea/physiology
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Hoegger Mark J
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.
Awadalla Maged
Namati Eman
Itani Omar A
Fischer Anthony J
Tucker Alexander J
Adam Ryan J
McLennan Geoffrey
Hoffman Eric A
Stoltz David A
Welsh Michael J
References (59)
59 references, click to expand
  1. Quantitative evaluation of the development of tracheal submucosal glands in infants with cystic fibrosis and control infants.
    Am J Pathol. 1982 Mar;106(3):303-11 PMID: 7065115
  2. Mucociliary clearance in cystic fibrosis.
    Pediatr Pulmonol. 2002 Apr;33(4):293-306 PMID: 11921459
  3. Loss of cystic fibrosis transmembrane conductance regulator function produces abnormalities in tracheal development in neonatal pigs and young children.
    Am J Respir Crit Care Med. 2010 Nov 15;182(10):1251-61 PMID: 20622026
  4. Local mucociliary defence mechanisms.
    Paediatr Respir Rev. 2000 Mar;1(1):27-34 PMID: 16263440
  5. Mucus properties in children with primary ciliary dyskinesia: comparison with cystic fibrosis.
    Chest. 2006 Jan;129(1):118-23 PMID: 16424421
  6. A comparative study of mammalian tracheal mucous glands.
    J Anat. 2000 Oct;197 Pt 3:361-72 PMID: 11117623
  7. High-dose lidocaine reduces airway mucus transport velocity in intubated anesthetized dogs.
    Respir Med. 2006 Feb;100(2):258-63 PMID: 15951162
  8. cAMP-activated Ca2+ signaling is required for CFTR-mediated serous cell fluid secretion in porcine and human airways.
    J Clin Invest. 2010 Sep;120(9):3137-48 PMID: 20739756
  9. Comparison of nonciliated tracheal epithelial cells in six mammalian species: ultrastructure and population densities.
    Exp Lung Res. 1983 Dec;5(4):281-94 PMID: 6662075
  10. Synergistic airway gland mucus secretion in response to vasoactive intestinal peptide and carbachol is lost in cystic fibrosis.
    J Clin Invest. 2007 Oct;117(10):3118-27 PMID: 17853942
  11. Heterogeneity of the composition and thickness of tracheal mucus in rats.
    Am J Physiol. 1997 Nov;273(5):L1036-41 PMID: 9374732
  12. Mucins, mucus, and sputum.
    Chest. 2009 Feb;135(2):505-512 PMID: 19201713
  13. Elastase contributes to antigen-induced mucociliary dysfunction in ovine airways.
    Am J Respir Crit Care Med. 1997 May;155(5):1522-8 PMID: 9154852
  14. Impairment of nasal mucociliary clearance in former smokers with stable chronic obstructive pulmonary disease relates to the presence of a chronic bronchitis phenotype.
    Rhinology. 2011 Oct;49(4):397-406 PMID: 21991564
  15. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome.
    Genet Med. 2009 Jul;11(7):473-87 PMID: 19606528
  16. The cells of the tracheobronchial epithelium of the mouse: a quantitative light and electron microscope study.
    J Anat. 1981 Jan;132(Pt 1):71-84 PMID: 7275793
  17. Modelling mucociliary clearance.
    Respir Physiol Neurobiol. 2008 Nov 30;163(1-3):178-88 PMID: 18439882
  18. Weight-carrying capacity and excitability of excised ciliated epithelium.
    Am J Physiol. 1948 Jan 1;152(1):1-5 PMID: 18903419
  19. Submucosal gland secretions in airways from cystic fibrosis patients have normal [Na(+)] and pH but elevated viscosity.
    Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8119-23 PMID: 11427704
  20. Airway mucus function and dysfunction.
    N Engl J Med. 2010 Dec 2;363(23):2233-47 PMID: 21121836
  21. Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia.
    Cell. 2010 Dec 10;143(6):911-23 PMID: 21145458
  22. Method for quantitative study of airway functional microanatomy using micro-optical coherence tomography.
    PLoS One. 2013;8(1):e54473 PMID: 23372732
  23. Microtubules enable the planar cell polarity of airway cilia.
    Curr Biol. 2012 Dec 4;22(23):2203-12 PMID: 23122850
  24. Optical method for quantifying rates of mucus secretion from single submucosal glands.
    Am J Physiol Lung Cell Mol Physiol. 2001 Aug;281(2):L458-68 PMID: 11435221
  25. Influence of particle size and material properties on mucociliary clearance from the airways.
    J Aerosol Med Pulm Drug Deliv. 2010 Aug;23(4):233-41 PMID: 20500091
  26. An investigation into the effects of midazolam and propofol on human respiratory cilia beat frequency in vitro.
    Intensive Care Med. 1998 Aug;24(8):791-4 PMID: 9757922
  27. Tracheal mucociliary transport rate in awake dogs.
    Am J Vet Res. 1993 Nov;54(11):1812-6 PMID: 8291756
  28. Tracheal mucociliary transport in patients with cystic fibrosis and its stimulation by terbutaline.
    Am Rev Respir Dis. 1975 Jun;111(6):733-8 PMID: 1137241
  29. Tracheal mucous transport in Beagles after long-term exposure to 1 ppm sulfur dioxide.
    Arch Environ Health. 1975 May;30(5):249-53 PMID: 1130839
  30. Estimation of tracheal mucous velocity by bronchofiberscopy.
    J Appl Physiol. 1973 Apr;34(4):495-9 PMID: 4698607
  31. The ΔF508 mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs.
    Sci Transl Med. 2011 Mar 16;3(74):74ra24 PMID: 21411740
  32. Submucosal glands and airway defense.
    Proc Am Thorac Soc. 2004;1(1):47-53 PMID: 16113412
  33. The porcine lung as a potential model for cystic fibrosis.
    Am J Physiol Lung Cell Mol Physiol. 2008 Aug;295(2):L240-63 PMID: 18487356
  34. Defective fluid secretion from submucosal glands of nasal turbinates from CFTR-/- and CFTR (ΔF508/ΔF508) pigs.
    PLoS One. 2011;6(8):e24424 PMID: 21935358
  35. Differential effects of intravenous anesthetics on ciliary motility in cultured rat tracheal epithelial cells.
    Can J Anaesth. 2006 Mar;53(3):242-9 PMID: 16527787
  36. Mucociliary transport in porcine trachea: differential effects of inhibiting chloride and bicarbonate secretion.
    Am J Physiol Lung Cell Mol Physiol. 2013 Feb 1;304(3):L184-90 PMID: 23204069
  37. Physiological basis of cystic fibrosis: a historical perspective.
    Physiol Rev. 1999 Jan;79(1 Suppl):S3-S22 PMID: 9922374
  38. Species differences in the physical and transport properties of airway secretions.
    Can J Physiol Pharmacol. 1995 Feb;73(2):165-71 PMID: 7621353
  39. Cystic fibrosis.
    N Engl J Med. 2005 May 12;352(19):1992-2001 PMID: 15888700
  40. Cystic fibrosis since 1938.
    Am J Respir Crit Care Med. 2006 Mar 1;173(5):475-82 PMID: 16126935
  41. Restoration of mucociliary transport in the fluid-depleted trachea by surface-active instillates.
    Am J Respir Cell Mol Biol. 2006 Apr;34(4):500-4 PMID: 16357366
  42. Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease.
    Cell. 1998 Dec 23;95(7):1005-15 PMID: 9875854
  43. Albuterol improves impaired mucociliary clearance after lung transplantation.
    J Heart Lung Transplant. 2007 Feb;26(2):138-44 PMID: 17258147
  44. Development of the airway epithelium and submucosal glands in the pig lung: changes in epithelial glycoprotein profiles.
    Br J Exp Pathol. 1986 Dec;67(6):821-9 PMID: 3801296
  45. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs.
    Science. 2008 Sep 26;321(5897):1837-41 PMID: 18818360
  46. Mucociliary clearance rates at various levels in dog lungs.
    Am Rev Respir Dis. 1970 Sep;102(3):388-97 PMID: 5450905
  47. Mucociliary interactions and mucus dynamics in ciliated human bronchial epithelial cell cultures.
    Am J Physiol Lung Cell Mol Physiol. 2011 Aug;301(2):L181-6 PMID: 21531774
  48. Histochemical identification of glycoproteins in pig bronchial epithelium: (a) normal and (b) hypertrophied from enzootic pneumonia.
    J Pathol. 1975 May;116(1):1-11 PMID: 1159572
  49. Propofol and methohexital have no significant effect on mucus secretion or clearance in the anesthetized dog.
    Crit Care Med. 2001 May;29(5):1045-8 PMID: 11378620
  50. Update of respiratory tract disease in children with primary ciliary dyskinesia.
    Proc Am Thorac Soc. 2011 Sep;8(5):438-43 PMID: 21926396
  51. Histological and ultrastructural observations on the development of the lung of the fetal pig.
    Acta Anat (Basel). 1976;95(2):218-33 PMID: 961354
  52. Effect of salmeterol on mucociliary and cough clearance in chronic bronchitis.
    Pulm Pharmacol Ther. 2006;19(2):96-100 PMID: 15970448
  53. The cytokines interleukin-1β and tumor necrosis factor-α stimulate CFTR-mediated fluid secretion by swine airway submucosal glands.
    Am J Physiol Lung Cell Mol Physiol. 2012 Aug 15;303(4):L327-33 PMID: 22683572
  54. The neonatal porcine lung: ultrastructural morphology and postnatal development of the terminal airways and alveolar region.
    Anat Rec. 1984 Oct;210(2):303-13 PMID: 6507895
  55. Evidence for airway surface dehydration as the initiating event in CF airway disease.
    J Intern Med. 2007 Jan;261(1):5-16 PMID: 17222164
  56. Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth.
    Sci Transl Med. 2010 Apr 28;2(29):29ra31 PMID: 20427821
  57. Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung.
    Nature. 2012 Jul 04;487(7405):109-13 PMID: 22763554
  58. Changes in mucociliary clearance during acute exacerbations of asthma.
    Am Rev Respir Dis. 1991 May;143(5 Pt 1):993-7 PMID: 2024856
  59. Initiation and maturation of cilia-generated flow in newborn and postnatal mouse airway.
    Am J Physiol Lung Cell Mol Physiol. 2009 Jun;296(6):L1067-75 PMID: 19346437
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
Published
2014-02-11
Epub
2014-00-28
Pages
2355-60
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC3926068
Subset
IM
Grants
NHLBI NIH HHS · HL051670 · United States
NHLBI NIH HHS · P01 HL091842 · United States
Howard Hughes Medical Institute · United States
NHLBI NIH HHS · HL091842 · United States
NIDDK NIH HHS · DK054759 · United States
NIDDK NIH HHS · P30 DK054759 · United States
NIGMS NIH HHS · T32 GM007337 · United States
NHLBI NIH HHS · DP2 HL117744 · United States
NHLBI NIH HHS · R01 HL112986 · United States
NHLBI NIH HHS · P01 HL051670 · United States
NIEHS NIH HHS · P30 ES005605 · United States
NHLBI NIH HHS · T32 HL007638 · United States
NCCDPHP CDC HHS · DP2 HL117744 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com