Roles of Mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases.
Roles of Mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases.
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DOI：
10.1016/j.jaci.2016.04.051
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Ali H
中科院分区：
文献类型：
--
作者：
Subramanian H;Gupta K;Ali H
肥大细胞（MC）是造血谱系的颗粒状组织驻留细胞，有助于血管稳态、先天/适应性免疫和伤口愈合。然而，MC最为人所知的是它们在过敏性和炎性疾病中的作用，如过敏反应、食物过敏、鼻炎、瘙痒、荨麻疹、特应性皮炎和哮喘。除了高亲和力IgE受体（FcεRI）外，MC还表达许多G蛋白偶联受体（GPCR），其是最大的膜受体蛋白组，并且是药物治疗的最常见靶点。抗微生物宿主防御肽（HDPs）、神经肽（NPs）、主要碱性蛋白（MBP）、嗜酸性粒细胞过氧化物酶（EPO）和许多FDA批准的肽能药物通过称为MAS相关G蛋白偶联受体-X2（MRGPRX 2;以前称为MrgX 2）的新型GPCR激活人MC。MRGPRX 2区别于其他GPCR的独特特征包括它们在质膜和细胞内位点上的存在以及它们在MC中的选择性表达。本文综述了MRGPRX 2在宿主防御、药物诱导的类过敏反应、神经源性炎症、疼痛、瘙痒以及慢性炎症性疾病如荨麻疹和哮喘中的作用。我们认为，直接杀死微生物并通过MRGPRX 2激活MC的HDP可以作为新的GPCR靶点来调节宿主对微生物感染的防御。此外，可以开发MRGPRX 2的单克隆抗体或小分子抑制剂用于治疗MC依赖性过敏性和炎症性疾病。
Mast cells (MCs), which are granulated tissue-resident cells of hematopoietic lineage, contribute to vascular homeostasis, innate/adaptive immunity and wound healing. MCs are, however, best known for their roles in allergic and inflammatory diseases such as anaphylaxis, food allergy, rhinitis, itch, urticaria, atopic dermatitis and asthma. In addition to the high affinity IgE receptor (FcεRI), MCs express numerous G protein coupled receptors (GPCRs), which are the largest group of membrane receptor proteins and are the most common targets of drug therapy. Antimicrobial host defense peptides (HDPs), neuropeptides (NPs), major basic protein (MBP), eosinophil peroxidase (EPO) and many FDA approved peptidergic drugs activate human MCs via a novel GPCR known as MAS-related G protein coupled receptor-X2 (MRGPRX2; formerly known as MrgX2). Unique features of MRGPRX2 that distinguish it from other GPCRs include their presence both on plasma membrane and intracellular sites and their selective expression in MCs. In this article, we review the possible roles of MRGPRX2 on host defense, drug-induced anaphylactoid reactions, neurogenic inflammation, pain, itch and chronic inflammatory diseases such as urticaria and asthma. We propose that HDPs that kill microbes directly and activate MCs via MRGPRX2 could serve as novel GPCR targets to modulate host defense against microbial infection. Furthermore, monoclonal antibodies or small molecule inhibitors of MRGPRX2 could be developed for the treatment of MC-dependent allergic and inflammatory disorders.
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影响因子：
12.4
作者：
Borici-Mazi, R;Kouridakis, S;Kontou-Fili, K
通讯作者：
Kontou-Fili, K
DOI：
10.1038/nri2782
发表时间：
2010-06
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
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作者：
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通讯作者：
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影响因子：
20.3
作者：
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影响因子：
14.2
作者：
BEDARD, PM;BRUNET, C;HEBERT, J
通讯作者：
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