The influence of cholinergic agents on histamine release from HMC-1 human mast cell line stimulated with IgG, C-reactive protein and compound 48/80

Aims: The aim of this work is to study the role of acetylcholine (ACh) receptors (AChRs) in the regulation of Fc gamma R activity in human mast cells (MC) activated by aggregated IgG (algG) and CRP. MC, the key regulators at the interface of innate and acquired immunity, have abundant Fc receptors for IgG (Fc gamma RII) which indicate the role of their ligands, IgG and C-reactive protein (CRP), in regulating MC activity. Cholinergic control of Fc gamma R-dependent MC functions is poorly defined. Main methods: HMC-1 culture of human MC; cell incubations with cholinergic drugs and Fc gamma R ligands such as heat aggregated human IgG or purified human CRP; compound 48/80, a known histamine liberator employing G protein-coupled receptors, was used as a positive control of MC degranulation; assessment of histamine release. Key findings: Both nAChR and mAChR antagonists (hexamethonium and methacine, respectively), per se, elevated histamine-releasing activity of the HMC-1 and suppressed the MC responses to most of investigated activators (carbachol, compound 48/80, and to a lesser extent algG). Two blockers together should be applied to algG-stimulated cells in order to obtain appreciable suppression of histamine release. The Fc gamma R-mediated HMC-1 cell response to CRP was the least sensitive to attenuation by ACh signaling. Significance: The data obtained suggest the involvement of ACh in the functioning of other receptor systems. Our results indicate that AChRs are closely associated with G protein-coupled receptor-induced reactions of MC and optionally with Fc gamma R-dependent functions. Conclusion: The data presented demonstrate that AChRs and endogenous ACh are involved in regulating mast cell degranulation and histamine release by affecting the functions of receptors to compound 48/80 and, less, Fc gamma Rs. (C) 2012 Elsevier Inc. All rights reserved.