Cholinergic modulation of mast cells

• Nadezhda A. Kutukova
• Alexander V. Polevshchikov

Abstract

Introduction. One of the aspects of inflammation control is the nervous and immune cooperation. Due to a wide range of activation receptors and mediators inherent in both systems, as well as anatomical colocalization with nerve fibers, mast cells (MC) are key intermediaries between these integrating systems and form bi-directional neuro-mastocytic functional units. The anti-inflammatory role of the vagus has been experimentally demonstrated. Its effects are mediated by the α7-nicotinic acetylcholine receptor but the question of cholinergic regulation of MC remains unclear.

The aim of the study was to evaluate the effect of acetylcholine (ACh) on MC secretory functions.

Material and methods. The source of MCs was mouse peritoneal exudate (PMC) cells. ACh has the dose-dependent effect on spontaneous and anti-IgE-induced degranulation of PTC which was evaluated by the level of histamine and β-hexosaminidase release in 5 and 15 min after ACh administration. To inhibit the binding of ACh to its α7-nicotonic receptor α-bungarotoxin (10^–6 M) was used.

Results. ACh caused degranulation of unstimulated PMCs. In 5 min after ACh adding (10^–5 M) into the cell cultures the maximum secretion-stimulating effect was observed (39 % for histamine and 47 % for β-hexosaminidase). In the contrary, after adding ACh to PTCs prestimulated by anti-IgE antibodies dose-depend reduction of secretion (-20–30 %) was observed. This inhibitory effect was canceled in the presence of α-bungarotoxin which suggests the involvement of the α7-nicotinic ACh receptor in signal transduction.

Conclusion. The ACh effect on MCs depends on the initial state of the system. In the case of unstimulated mastocytes ACh promotes their degranulation and secretion of preformed mediators. On the contrary, in the framework of the immune response ACh can inhibit the MC activation to prevent their massive degranulation.

Keywords: mast cells; neuroimmune communication; mast cell-nerve functional unit, acetylcholine; histamine; cholinergic anti-inflammatory pathway

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