Cholinergic brush cells in the trachea mediate respiratory responses to quorum sensing molecules

Life Sci. 2012 Nov 27;91(21-22):992-6. doi: 10.1016/j.lfs.2012.06.014. Epub 2012 Jun 28.


Aim: The airway epithelial surface is constantly exposed to inhaled environmental factors and pathogens. Bitter "tasting" bacterial products such as quorum sensing molecules (QSM) can be detected by solitary chemosensory cells of the upper respiratory tract. Recently, we have shown that tracheal brush cells are cholinergic chemosensory cells affecting the respiration upon stimulation with bitter substances. Here, we explore the hypothesis that tracheal brush cells are capable of detection of bacterial products such as QSM resulting in changes in respiration and in induction of local effects, e.g. regulation of mucociliary clearance.

Main methods: Functional analyses of respiration were performed in the trachea using a newly established model for investigation of respiration in spontaneously breathing anesthetized mice upon isolated tracheal stimulation. Influence of N-3-oxododecanoyl-homoserine lactone (3-OxoC(12)-HSL) on cilia-driven particle transport speed (PTS) in the airways was investigated in acutely excised and submerged mouse tracheae.

Key findings: 3-OxoC(12)-HSL, a Pseudomonas aeruginosa quorum sensing autoinducer, caused a drop in the respiratory rate 2 min after the application at the mucosal surface. The 3-OxoC(12)-HSL-induced effect on respiration was abolished by inhibition of nicotinic receptors with mecamylamine and by removal of the respiratory epithelium. At the same concentration, 3-OxoC(12)-HSL enhanced significantly PTS on the mucosal surface.

Significance: We conclude that cholinergic airway epithelial cells sense bacterial QSM in the airway lining fluid and communicate this to the CNS via ACh release and nicotinic stimulation of sensory neurons. In addition, QSM enhance PTS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / administration & dosage
  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / metabolism
  • Animals
  • Homoserine / administration & dosage
  • Homoserine / analogs & derivatives*
  • Homoserine / metabolism
  • Host-Pathogen Interactions*
  • Male
  • Mecamylamine / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Nicotinic Antagonists / pharmacology
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / physiology*
  • Quorum Sensing*
  • Receptors, Nicotinic / metabolism*
  • Respiration / drug effects
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / microbiology
  • Trachea / cytology
  • Trachea / drug effects
  • Trachea / microbiology*


  • N-(3-oxododecanoyl)homoserine lactone
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Mecamylamine
  • Homoserine
  • 4-Butyrolactone