Mast cell-cholinergic nerve interaction in mouse airways.
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.
Weigand
Letitia A
LA
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Myers
Allen C
AC
Meeker
Sonya
S
Undem
Bradley J
BJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D002799:Cholinergic Fibers / Q000502:physiology*; D055724:Electrophysiological Phenomena; D006636:Histamine Release; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000276:immunology / Q000294:innervation* / Q000502:physiology*
D018727:Muscarinic Antagonists; D012702:Serotonin Antagonists; D012701:Serotonin; D001285:Atropine; D010047:Ovalbumin; D007650:Ketanserin