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首页> 外文期刊>Cellular immunology >Mivacurium induce mast cell activation and pseudo-allergic reactions via MAS-related G protein coupled receptor-X2
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Mivacurium induce mast cell activation and pseudo-allergic reactions via MAS-related G protein coupled receptor-X2

机译：Mivacurium诱导肥大细胞活化和伪过敏反应通过MAS相关的G蛋白偶联受体-X2

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BackgroundMivacurium is a non-depolarizing muscle relaxant and widely used as a short-acting anesthetic. Pseudo-allergic reactions to mivacurium occur when it is administered during perioperative anesthesia. These reactions may present a serious threat to the patient’s life, particularly in children. MethodsMAS-related G protein coupled receptor-related pseudo-allergic reactions that were induced by mivacurium were investigated using skin swelling and extravasation assaysin vivoand mast cell degranulation assayin vitro. ResultsMivacurium caused pseudo-allergic reactions in wild-type mice by inducing mast cells to release histamine. However, it did not induce a similar phenomenon in KitW-sh/W-shmice. Furthermore, MrgprB2-knockout mice displayed no inflammatory response to mivacurium. Mivacurium induced LAD2 cell degranulation in a dose-dependent manner. Mivacurium stimulated intracellular calcium ion (Ca2+) influx in MRGPRX2-HEK293 cells but not in NC-HEK293 cells. However, mivacurium induced the release of only low levels of mediators in LAD2 cells transfected with MRGPRX2-targeted small interfering (si)RNA. Notably, cytokine release was not observed in LAD2 cells even when stimulated with high concentrations of mivacurium. ConclusionMivacurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. However, mivacurium did not induce the release of other cytokines. Therefore, the targeting of MRGPRX2 can potentially block mivacurium-induced adverse drug effects, particularly pseudo-allergic reactions.
机译：背景氨基乙酸是一种非去极化的肌肉松弛剂，广泛用作短作用麻醉剂。在围手术期麻醉期间施用时发生对酰乙酸的伪过敏反应。这些反应可能对患者的生命产生严重威胁，特别是在儿童中。方法采用皮肤溶胀和外渗分析诱导型肥大肥豆细胞溶解蛋白酶促进与Mivaccarium诱导的含有Mivaccarium诱导的受体相关的受体相关的伪过敏反应。结果制剂通过诱导肥大细胞引起野生型小鼠中的伪过敏反应以释放组胺。然而，它没有诱导Kitw-SH / W-Shmice中类似的现象。此外，MRGPRB2-NOCKOUT小鼠对Mivacurium没有显示出炎症反应。 Mivaccarium诱导Lad2细胞以剂量依赖性方式脱粒。 Mivacurium刺激MRGPRX2-HEK293细胞中的细胞内钙离子（CA2 +）流入，但不在NC-HEK293细胞中。然而，Mivacurium诱导仅在用MRGPRX2靶向小干扰（Si）RNA转染的LAD2细胞中仅释放低水平的介质。值得注意的是，即使用高浓度的Mivaccarium刺激，在Lad2细胞中未观察到细胞因子释放。结论MIVARACURIUM活化MRGPRX2和触发肥大细胞脱粒，导致过敏反应。然而，Mivacurium没有诱导其他细胞因子的释放。因此，MRGPRX2的靶向可以妨碍诱导致癌的不利药物作用，特别是伪过敏反应。

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