Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling

•Acetylcholine promotes airway inflammation and remodeling via M3 receptors. •Airway nerves regulate airway hyper-responsiveness and inflammation. •Bronchoconstriction might be an alternative driver of airway remodeling. •Both neuronal and non-neuronal acetylcholine contribute to airway inflammation and remodeling. Acetylcholine is the primary parasympathetic neurotransmitter in the airways, where it not only induces bronchoconstriction and mucus secretion, but also regulates airway inflammation and remodeling. In this review, we propose that these effects are all primarily mediated via the muscarinic M3 receptor. Acetylcholine promotes inflammation and remodeling via direct effects on airway cells, and via mechanical stress applied to the airways sequential to bronchoconstriction. The effects on inflammation and remodeling are regulated by both neuronal and non-neuronal acetylcholine. Taken together, we believe that the combined effects of anticholinergic therapy on M3-mediated bronchoconstriction, mucus secretion, inflammation, and remodeling may account for the positive outcome of treatment with these drugs for patients with chronic pulmonary obstructive disease (COPD) or asthma. Acetylcholine is the primary parasympathetic neurotransmitter in the airways, where it not only induces bronchoconstriction and mucus secretion, but also regulates airway inflammation and remodeling. In this review, we propose that these effects are all primarily mediated via the muscarinic M3 receptor. Acetylcholine promotes inflammation and remodeling via direct effects on airway cells, and via mechanical stress applied to the airways sequential to bronchoconstriction. The effects on inflammation and remodeling are regulated by both neuronal and non-neuronal acetylcholine. Taken together, we believe that the combined effects of anticholinergic therapy on M3-mediated bronchoconstriction, mucus secretion, inflammation, and remodeling may account for the positive outcome of treatment with these drugs for patients with chronic pulmonary obstructive disease (COPD) or asthma. a primary parasympathetic neurotransmitter in the airways, where it induces bronchoconstriction and mucus secretion via muscarinic receptors, and a hormone released from non-neuronal cells. structural changes that occur in both large and small airways in airway diseases, including asthma and COPD. muscarinic receptor antagonists used for the treatment of COPD and, to a lesser extent, asthma, to inhibit the effects of acetylcholine. a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. a chronic inflammatory disorder of the airways associated with airflow limitation that is usually progressive. increase of the number of eosinophils, which are leukocytes involved in the allergic asthmatic response. the volume of air that can forcibly be blown out in 1 s after full inspiration. major component of the outer membrane of Gram-negative bacteria, which generates an inflammatory response. G protein-coupled receptors that are expressed by almost all cell types in the airways and are target receptors for acetylcholine. increase in the number of neutrophils, which are granulocytes involved in the inflammatory response in COPD. an index designed to measure and quantify health status in patients with chronic airflow limitation.