Laboratory of General Immunology, Institute of Experimental Medicine, 12 Acad. Pavlov Street, St. Petersburg 197376, Russia.
Life Sci. 2012 Nov 27;91(21-22):1053-7. doi: 10.1016/j.lfs.2012.08.004. Epub 2012 Aug 11.
The aim of this work is to study the role of acetylcholine (ACh) receptors (AChRs) in the regulation of FcγR activity in human mast cells (MC) activated by aggregated IgG (aIgG) and CRP. MC, the key regulators at the interface of innate and acquired immunity, have abundant Fc receptors for IgG (FcγRII) which indicate the role of their ligands, IgG and C-reactive protein (CRP), in regulating MC activity. Cholinergic control of FcγR-dependent MC functions is poorly defined.
HMC-1 culture of human MC; cell incubations with cholinergic drugs and FcγR 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.
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 aIgG). Two blockers together should be applied to aIgG-stimulated cells in order to obtain appreciable suppression of histamine release. The FcγR-mediated HMC-1 cell response to CRP was the least sensitive to attenuation by ACh signaling.
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 FcγR-dependent functions.
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, FcγRs.
本研究旨在探讨乙酰胆碱（ACh）受体（AChRs）在人肥大细胞（MC）中调节 FcγR 活性的作用，这些 MC 由聚集 IgG（aIgG）和 C 反应蛋白（CRP）激活。MC 作为先天和获得性免疫的关键调节者，具有丰富的 IgG（FcγRII）Fc 受体，表明其配体 IgG 和 C 反应蛋白（CRP）在调节 MC 活性中的作用。胆碱能对 FcγR 依赖性 MC 功能的控制作用尚未明确。
人 MC 的 HMC-1 培养；细胞与胆碱能药物和 FcγR 配体（如热聚合人 IgG 或纯化人 CRP）孵育；已知通过 G 蛋白偶联受体释放组胺的化合物 48/80 用作 MC 脱颗粒的阳性对照；评估组胺释放。
两种烟碱型乙酰胆碱受体（nAChR）和毒蕈碱型乙酰胆碱受体（mAChR）拮抗剂（六烃季铵和甲磺酸，分别）本身就可提高 HMC-1 的组胺释放活性，并抑制 MC 对大多数研究激活剂（乙酰胆碱、化合物 48/80，以及在较小程度上 aIgG）的反应。为了获得组胺释放的明显抑制，应将两种阻断剂一起应用于 aIgG 刺激的细胞。FcγR 介导的 HMC-1 细胞对 CRP 的反应对乙酰胆碱信号的衰减最不敏感。
获得的数据表明 ACh 参与了其他受体系统的功能。我们的结果表明，AChRs 与 G 蛋白偶联受体诱导的 MC 反应密切相关，并且与 FcγR 依赖性功能有关。
本研究结果表明，AChRs 和内源性 ACh 通过影响化合物 48/80 和 FcγR 的功能，参与调节肥大细胞脱颗粒和组胺释放。
