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Embryonic Chicken Trachea as a New In Vitro Model for the Investigation of Mucociliary Particle Clearance in the Airways

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Abstract

Mucociliary clearance (MC) is an important defense mechanism of the respiratory system to eliminate inhaled and possibly noxious particles from the lung. Although the principal mechanics of MC seem to be relatively clear there are still open questions regarding the long-term clearance of particles. Therefore, we have developed a new set-up based on embryonic chicken trachea (ECT) to investigate mucociliary particle clearance in more detail. ECT was placed in an incubation chamber after carbon particles were applied and tracked using optical microscopy. The aim of the study was to validate this model by investigating the impact of temperature, humidity and drugs on particle transport rates. Particles were transported reproducibly along the trachea and clearance velocity (2.39 ± 0.25) mm/min was found to be in accordance to data reported in literature. Variation in temperature resulted in significantly reduced MC: (0.40 ± 0.12) mm/min (20 °C); (0.42 ± 0.10) mm/min (45 °C). Decreasing humidity (99–60%) had no significant effect on MC, whereas reduction to 20% humidity showed a significant influence on particle clearance. The use of different cilio- and muco-active drugs (Propranolol, Terbutalin, N-acetylcysteine) resulted in altered MC according to the pharmacological effect of the substances: a concentration dependent decrease of MC was found for Propranolol. From our results we conclude that this model can be employed to investigate MC of particles in more detail. Hence, the model may help to understand and identify decisive physico-chemical parameters for MC and to answer open questions regarding the long-term clearance phenomenon.

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Acknowledgements

Leon Muijs and Beat Haenni are thanked for technical support and introduction to SEM/TEM imaging. Gregor Jung and Babette Hinkeldey are thanked for cover slip modification for the incubation chamber.

Financial support from the Federal German Ministry of Education and Research is gratefully acknowledged (Nano-Inhale-13N8890).

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Authors and Affiliations

  1. Biopharmaceutics and Pharmaceutical Technology, Saarland University, P.O. Box 15 11 50, 66041, Saarbrücken, Germany

    A. Henning, M. Schneider, M. Bur & C.-M. Lehr

  2. Institute of Anatomy, University of Bern, Bern, Switzerland

    F. Blank & P. Gehr

  3. Pharmaceutical Nanotechnology, Saarland University, Saarbruecken, Germany

    M. Schneider

Authors
  1. A. Henning
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  2. M. Schneider
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  3. M. Bur
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  4. F. Blank
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  5. P. Gehr
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  6. C.-M. Lehr
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Correspondence to C.-M. Lehr.

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Video 1

Exemplary video for mucociliary clearance of carbon particles. Particles are clearly and reproducibly transported on the tracheal tissue. Particle clearance is unidirectional and always to the proximal end of the trachea. Visualization and tracking of the carbon particles was realized by transition light microscopy. (×100, top view; MPG 2.78 MB)

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Henning, A., Schneider, M., Bur, M. et al. Embryonic Chicken Trachea as a New In Vitro Model for the Investigation of Mucociliary Particle Clearance in the Airways. AAPS PharmSciTech 9, 521–527 (2008). https://doi.org/10.1208/s12249-008-9072-6

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