Increase of Mast Cell-Nerve Association and Neuropeptide Receptor Expression on Mast Cells in Perennial Allergic Rhinitis

Abstract

Objectives: Mast cells (MCs) and nerves play an important role in allergic rhinitis (AR), but little is known about their crosstalk in AR. The aim of this study was to investigate MC-nerve interaction in the human nasal mucosa during AR. Methods: The association between MCs and nerves, the expression of neuropeptide receptors (neurokinin 1 receptor [NK1R], neurokinin 2 receptor [NK2R], calcitonin gene-related peptide receptor [CGRPR], and MrgX2) on MCs, and protease-activated receptor 2 (PAR2) and tyrosine receptor kinase A (TrkA) on nerve fibres in the human nasal mucosa were investigated with immunofluorescence and real-time PCR. Results: The association between MCs and nerves was found to be significantly increased, although the numbers of MCs and nerve fibres were unchanged during AR. MCs expressing tryptase-chymase (MC_tc) were frequently associated with nerve fibres and these contacts increased significantly in AR. Neuropeptide receptors NK1R, NK2R, and CGRPR were firstly found to be largely localised on MCs. The number of MCs expressing NK1R and NK2R, but not CGRPR, was significantly increased in AR. Interestingly, MC_tc mostly expressed these neuropeptide receptors. The newly discovered tachykinin receptor MrgX2 was not expressed on nasal MCs, but was expressed on gland cells and increased in AR. Additionally, tachykinergic nerve fibres were found to express PAR2 or TrkA as receptors for MCs. Conclusions: This study revealed for the first time an increase of MC-nerve association and neuropeptide receptor expression on MCs during AR as well as nerve fibres containing receptors for MCs. These results suggest that targeting or controlling airway sensory nerve function as a modulator of MCs may prevent allergic airway inflammation such as AR.

Decreased Migration of Dendritic Cells into the Jugular-Nodose Ganglia by the CXCL12 Neutraligand Chalcone 4 in Ovalbumin-Sensitized Asthmatic Mice

“…Airway vagal sensory neurons play a pivotal role in the neurogenic inflammation of the airways [11] via neuronal reflex and by triggering the release of a variety of neuropeptides [29]. We showed here that the increased DC/neuron ratio in the OVA compared to the saline groups was identical in this OVA model as in the house dust mite model previously reported [11].…”

Non‐IgE mediated mast cell activation

“…Early studies using NK‐1R KO mice showed that the neurokinin receptor‐1 (NK‐1R) was necessary to induce MC‐dependent edema formation . Its expression was inducible in cultured BMMC by IL4 and SCF or in nasal mucosa MC during allergic rhinitis, which may be relevant in inflammatory conditions . Interestingly, new studies found that SP also interacts with MRGPRX2 albeit with somewhat lower affinity (0.5 nM vs 100 nM) and much lower affinity (50 μM) in the case of mouse MRGPRB2 .…”

The role and relevance of mast cells in urticaria

“…Human skin mast cells express the G‐protein coupled receptor (GPCR) mas‐related gene X2 (MrgX2) that allows them to be activated for degranulation by polybasic substances, such as compound 48/80 and poly‐L‐lysine . Mast cells also express neuropeptide receptors, such as neurokinin 1 and 2 receptors (NK1R and NK2R), calcitonin gene‐related peptide receptor (CGRPR), and the neurotrophin receptors, tropomyosin‐related kinase A (TrkA), TrkB, and TrkC . Neuropeptides such as substance P, vasoactive intestinal peptide (VIP), and somatostatin, but not eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene‐related peptide (CGRP) stimulate both mast cell degranulation and cytokine production .…”