Mast cell-cholinergic nerve interaction in mouse airways

J Physiol. 2009 Jul 1;587(Pt 13):3355-62. doi: 10.1113/jphysiol.2009.173054. Epub 2009 Apr 29.

Abstract

We addressed the mechanism by which antigen contracts trachea isolated from actively sensitized mice. Trachea were isolated from mice (C57BL/6J) that had been actively sensitized to ovalbumin (OVA). OVA (10 microg ml(-1)) caused histamine release (approximately total tissue content), and smooth muscle contraction that was rapid in onset and short-lived (t(1/2) < 1 min), reaching approximately 25% of the maximum tissue response. OVA contraction was mimicked by 5-HT, and responses to both OVA and 5-HT were sensitive to 10 microm-ketanserin (5-HT(2) receptor antagonist) and strongly inhibited by atropine (1microm). Epithelial denudation had no effect on the OVA-induced contraction. Histological assessment revealed about five mast cells/tracheal section the vast majority of which contained 5-HT. There were virtually no mast cells in the mast cell-deficient (sash -/-) mouse trachea. OVA failed to elicit histamine release or contractile responses in trachea isolated from sensitized mast cell-deficient (sash -/-) mice. Intracellular recordings of the membrane potential of parasympathetic neurons in mouse tracheal ganglia revealed a ketanserin-sensitive 5-HT-induced depolarization and similar depolarization in response to OVA challenge. These data support the hypothesis that antigen-induced contraction of mouse trachea is epithelium-independent, and requires mast cell-derived 5-HT to activate 5-HT(2) receptors on parasympathetic cholinergic neurons. This leads to acetylcholine release from nerve terminals, and airway smooth muscle contraction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Bronchoconstriction / drug effects
  • Bronchoconstriction / physiology
  • Cholinergic Fibers / physiology*
  • Electrophysiological Phenomena
  • Histamine Release
  • In Vitro Techniques
  • Ketanserin / pharmacology
  • Male
  • Mast Cells / immunology
  • Mast Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscarinic Antagonists / pharmacology
  • Muscle Contraction / drug effects
  • Muscle Contraction / immunology
  • Muscle Contraction / physiology
  • Ovalbumin / immunology
  • Serotonin / physiology
  • Serotonin Antagonists / pharmacology
  • Trachea / drug effects
  • Trachea / immunology
  • Trachea / innervation*
  • Trachea / physiology*

Substances

  • Muscarinic Antagonists
  • Serotonin Antagonists
  • Serotonin
  • Atropine
  • Ovalbumin
  • Ketanserin