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

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 (MCtc) 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, MCtc 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.