BAUS 2020 abstracts: P3-5 mast cells express the mast cell related G-protein coupled receptor X2 (MRGPRX2) in the urinary bladders of interstitial cystitis/bladder pain syndrome patients: potential role in the pathogenesis of neurogenic inflammation

Abdelwahab, O., Markham, H., Yushuh, M., Garba, K., Bodey, K., Birch, B., Lwaleed, B., Johnston, D. and Walls, A. (2020) BAUS 2020 abstracts: P3-5 mast cells express the mast cell related G-protein coupled receptor X2 (MRGPRX2) in the urinary bladders of interstitial cystitis/bladder pain syndrome patients: potential role in the pathogenesis of neurogenic inflammation. Journal of Clinical Urology, 13 (1 Suppl.), [P3-5]. (doi:10.1177/2051415820963006).

Abstract

Background: mast cells numbers and activity are significantly elevated in the bladders of patients with interstitial cystitis (IC/BPS). This condition is associated with an increased density of the bladder sensory nerve endings, which release neuroactive substances, e.g. substance P (SP), thereby inducing mast cell degranulation and tissue inflammation. However, the responsiveness of mast cells to SP is variable between different tissues depending on the local cellular micro-environment.

MRGPRX2 is a recently identified G-protein coupled receptor involved in mast cell responsiveness to SP in different chronic inflammatory conditions, and its expression is associated with increased tissue inflammation.

Problem: the responsiveness of the urinary bladder mast cells to SP has not yet been explored, which makes theories related to neurogenic inflammation in the pathogenesis of BPS/IC uncertain. In the current study, we investigated the potential responsiveness of the bladder mast cells to the neuropeptide SP. For such purpose, urinary bladder biopsies, from 32 consented BPS/IC patients, were serially sectioned and stained with antibodies for the mast cell-specific proteases (Tryptase and Chymase), in addition to MRGPRX2.

Outcome: 30 out of 32 BPS/IC biopsies consistently co-expressed MRGPRX2 as well as Tryptase and chymase, in the lamina propria and detrusor layers of the bladder wall, indicating positive responsiveness of the bladder mast cells to SP.

Learning: neurogenic inflammation caused by the SP-induced mast cell degranulation is a potential driving engine for the chronic tissue inflammation in BPS/IC patients. Blocking SP- MRGPRX2 signalling could potentially alleviate longstanding bladder inflammation and pain in this group of patients.

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Contributors

Author: O. Abdelwahab

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