Dual Effects of Acetylcholine on Mast Cell–Nerve Interactions

Mast cell (MC)-nerve units are one of the main elements of cooperation between the nervous and immune systems, providing a structural and functional connection between MCs and autonomic nerve fibers. Although immunoregulatory activity of acetylcholine (ACh) is well established, the exact point of its influence on MCs remains unclear. This study compared the effects of muscarinic (mAChR) versus nicotinic (nAChR) ACh receptor binding on secretory activity of HMC-1 cells. It was found that ACh activates intact MCs mainly through the M3 mAChR, but suppresses degranulation in stimulated MCs via the α7 nAChR. The findings indicate that changes in the receptor pattern within MC-nerve units underlie the dual effects of ACh and enable MCs to switch functions in inflammation from proinflammatory activity in the acute phase to anti-inflammatory activity during reparation.