Non-neuronal cholinergic airway epithelium biology

Acetylcholine, a major regulator of airway function, is not solely produced by neurons but also by a variety of non-neurons cells including various airway epithelial cells utilizing a molecular machinery of acetylcholine synthesis and release that differs from that of neurons. While canonical neuronal cholinergic signaling pathways, for example, nerve driven bronchoconstriction, are still valid, new pathways of cholinergic communication have emerged which center around innate immunity. These include cholinergic luminal signaling via the airway lining fluid to reach receptors at the apical side of epithelial cells and on macrophages patrolling on the surface, and preneuronal cholinergic signaling where sensory neurons are the target of ACh released from a recently identified chemosensory cell that monitors the airway lining fluid for the presence of potentially hazardous compounds utilizing the classical taste transduction cascade.