肥大细胞相关G蛋白偶联受体介导神经源性炎症反应及宿主防御作用

Mas-related G protein-coupled receptors mediate neurogenic inflammation and pain responses and host defense and microbial clearance

肥大细胞在炎症和过敏反应中发挥重要作用,除了高亲和力的免疫球蛋白E(Immunoglobulin E,IgE)受体FcεRI外,肥大细胞还表达大量的G蛋白偶联受体(G-protein-coupled receptors,GPCRs),这是最大的膜受体蛋白群,也是药物治疗中最常见的靶点。肥大细胞相关的G蛋白偶联受体X2(Mas-related G protein-coupled receptors X2,MrgprX2)是一种具有多种配体的内源性受体,在肥大细胞中选择性表达。抗菌宿主防御肽、神经肽、碱性蛋白、嗜酸性粒细胞过氧化物酶和许多美国食品和药物管理局(Food and Drug Administration,FDA)批准的肽类药物可通过该受体独立激活肥大细胞,引起肥大细胞脱颗粒和促炎介质的释放,并促进多细胞信号级联。MrgprX2在宿主防御、药物诱导的过敏性反应、神经源性炎症、疼痛、瘙痒和慢性炎症性疾病中发挥作用,是治疗多种疾病的潜在靶点。

Mast cells play an important role in inflammation and allergic reactions.In addition to the high-affinity IgE receptor FcεRI,mast cells also express a large number of G-protein-coupled receptors(GPCRs),which are the largest group of membrane receptor proteins and the most common target in drug therapy.Mas-related G protein-coupled receptors X2(MrgprX2)is an endogenous receptor with a variety of ligands and is selectively expressed in mast cells.Antimicrobial host defense peptides,neuropeptides,basic proteins,eosinophil peroxidase,and many FDA-approved peptide drugs independently activate mast cells through this receptor,causing mast cell degranulation and the release of pro-inflammatory mediators,and promoting multicellular signaling cascaves.MrgprX2 plays a role in host defense,drug-induced allergic reactions,neurogenic inflammation,pain,itching,and chronic inflammatory diseases,and is a potential target for the treatment of a variety of diseases.