Intravital imaging of mucus transport in asthmatic mice using microscopic optical coherence tomography

Am J Physiol Lung Cell Mol Physiol. 2022 Oct 1;323(4):L423-L430. doi: 10.1152/ajplung.00455.2021. Epub 2022 Aug 23.

Abstract

Asthma is one of the most common chronic diseases. Mucus overproduction is consistently linked to asthma morbidity and mortality. Despite the knowledge of the importance of mucus, little data exist on how mucus is transported in asthma and the immediate effects of therapeutic intervention. We therefore used microscopic optical coherence tomography (mOCT) to study spontaneous and induced mucus transport in an interleukin-13 (IL-13)-induced asthma mouse model and examined the effects of isotonic (0.9% NaCl) and hypertonic saline (7% NaCl), which are used to induce mucus transport in cystic fibrosis. Without intervention, no bulk mucus transport was observed by mOCT and no intraluminal mucus was detectable in the intrapulmonary airways by histology. Administration of ATP-γ-S induced mucus secretion into the airway lumen, but it did not result in bulk mucus transport in the trachea. Intraluminal-secreted immobile mucus could be mobilized by administration of isotonic or hypertonic saline but hypertonic saline mobilized mucus more reliably than isotonic saline. Irrespective of saline concentration, the mucus was transported in mucus chunks. In contrast to isotonic saline solution, hypertonic saline solution alone was able to induce mucus secretion. In conclusion, mOCT is suitable to examine the effects of mucus-mobilizing therapies in vivo. Although hypertonic saline was more efficient in inducing mucus transport, it induced mucus secretion, which might explain its limited benefit in patients with asthma.

Keywords: OCT; asthmatic mice; hypertonic saline; mucus transport; trachea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate
  • Animals
  • Asthma* / diagnostic imaging
  • Asthma* / drug therapy
  • Interleukin-13*
  • Intravital Microscopy
  • Mice
  • Mucus
  • Saline Solution
  • Saline Solution, Hypertonic / pharmacology
  • Saline Solution, Hypertonic / therapeutic use
  • Sodium Chloride
  • Tomography, Optical Coherence

Substances

  • Interleukin-13
  • Saline Solution
  • Saline Solution, Hypertonic
  • Sodium Chloride
  • Adenosine Triphosphate

Associated data

  • figshare/10.6084/m9.figshare.16940371
  • figshare/10.6084/m9.figshare.16940380
  • figshare/10.6084/m9.figshare.16940377
  • figshare/10.6084/m9.figshare.16940374
  • figshare/10.6084/m9.figshare.16940368
  • figshare/10.6084/m9.figshare.19825825.v1