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Mivacurium induce mast cell activation and pseudo-allergic reactions via MAS-related G protein coupled receptor-X2

Delu Che1, Jue Wang1, Yuanyuan Ding1

  • 1College of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.

Cellular Immunology
|August 20, 2018
PubMed
Abstract

Insights

Mivacurium, a short-acting anesthetic, can cause pseudo-allergic reactions by activating MRGPRX2 and mast cells. Targeting MRGPRX2 may prevent these dangerous anaphylactoid reactions.

Area of Science:

  • Pharmacology
  • Immunology
  • Cell Biology

Background:

  • Mivacurium is a non-depolarizing muscle relaxant used in anesthesia.
  • Pseudo-allergic reactions to mivacurium can be life-threatening, especially in pediatric patients.
  • These reactions are associated with perioperative administration.

Purpose of the Study:

  • To investigate the mechanisms of mivacurium-induced pseudo-allergic reactions.
  • To identify the specific receptor involved in mivacurium-induced mast cell activation.
  • To explore potential therapeutic targets for mitigating adverse drug reactions.

Main Methods:

  • In vivo studies using wild-type and genetically modified mice (KitW-sh/W-sh, MrgprB2-knockout).
  • In vitro assays including mast cell degranulation (LAD2 cells) and calcium ion influx studies (MRGPRX2-HEK293 cells).
  • Use of small interfering RNA (siRNA) to target MRGPRX2 in LAD2 cells.

Main Results:

  • Mivacurium induced histamine release from mast cells in wild-type mice, but not in KitW-sh/W-sh or MrgprB2-knockout mice.
  • Mivacurium triggered dose-dependent degranulation of LAD2 cells and calcium influx in MRGPRX2-HEK293 cells.
  • Targeting MRGPRX2 with siRNA reduced mediator release, and no significant cytokine release was observed.

Conclusions:

  • Mivacurium activates MRGPRX2, leading to mast cell degranulation and anaphylactoid reactions.
  • The primary mechanism involves MRGPRX2 activation, not broad cytokine release.
  • Targeting MRGPRX2 presents a potential strategy to prevent mivacurium-induced pseudo-allergic adverse drug effects.
Keywords:
CytokineLAD2 mast cellMRGPRX2MivacuriumPseudo-allergic reactions

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