Cooperation between mast cells and neurons is essential for antigen-mediated bronchoconstriction.
Mast cells are important sentinels guarding the interface between the environment and the body: a breach in the integrity of this interface can lead to the release of a plethora of mediators that engage the foreign agent, recruit leukocytes, and initiate adaptive physiological changes in the organism. While these capabilities make mast cells critical players in immune defense, it also makes them important contributors to the pathogenesis of diseases such as asthma. Mast cell mediators induce dramatic changes in smooth muscle physiology, and the expression of receptors for these factors by smooth muscle suggests that they act directly to initiate constriction. Contrary to this view, we show herein that mast cell-mediated bronchoconstriction is observed only in animals with intact innervation of the lung and that serotonin release alone is required for this action. While ablation of sensory neurons does not limit bronchoconstriction, constriction after Ag challenge is absent in mice in which the cholinergic pathways are compromised. Linking mast cell function to the cholinergic system likely provides an important means of modulating the function of these resident immune cells to physiology of the lung, but may also provide a safeguard against life-threatening anaphylaxis during mast cell degranulation.
Cyphert
Jaime M
JM
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Kovarova
Martina
M
Allen
Irving C
IC
Hartney
John M
JM
Murphy
Dennis L
DL
Wess
Jürgen
J
Koller
Beverly H
BH
D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D016084:Bronchoconstriction / Q000276:immunology* / Q000502:physiology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000276:immunology*; D012701:Serotonin / Q000378:metabolism; D014628:Vagotomy
D000941:Antigens; D012701:Serotonin