MRGPRX2 is essential for sinomenine hydrochloride induced anaphylactoid reactions

被引:55
|
作者
Liu, Rui [1 ,2 ]
Che, Delu [1 ]
Zhao, Tingting [1 ]
Pundir, Priyanka [2 ]
Cao, Jiao [1 ]
Lv, Yanni [1 ]
Wang, Jue [1 ]
Ma, Pengyu [1 ]
Fu, Jia [1 ]
Wang, Nana [1 ]
Wang, Xiaoyang [1 ]
Zhang, Tao [1 ]
Dong, Xinzhong [2 ]
He, Langchong [1 ]
机构
[1] Xi An Jiao Tong Univ, Sch Pharm, Yanta West Rd, Xian 710061, Shaanxi, Peoples R China
[2] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA
基金
中国国家自然科学基金;
关键词
Sinomenine hydrochloride (SH); Mast cell; MRGPRX2; Degranulation; Anaphylactoid reactions; MAST-CELL; UP-REGULATION; ACTIVATION; DEGRANULATION; SECRETAGOGUES; PHARMACOLOGY; RELEASE; BETA;
D O I
10.1016/j.bcp.2017.09.017
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Mast cells are unique immunocytes that function as sentinel cells in host defense reactions such as immediate hypersensitivity responses and anaphylactic responses. The mast cell specific receptor MRGPRX2 (Mas-related G protein-coupled receptor X2) triggers mast cell degranulation-a key process in anaphylactic reactions. We sought to better understand anaphylactic reaction induced by sinomenine hydrochloride (SH). MRGPRX2-related pseudo-allergic reactions induced by SH were investigated using the hindpaw swelling and extravasation assay in vivo and mast cell degranulation assays in vitro. MrgprB2 knockout mice exhibit a reduced SH-induced inflammation effect. Furthermore, MRGPRX2 (the orthologous gene of MrgprB2) related human mast cells are activated by SH in a dose-dependent manner; however, MRGPRX2 knockdown mast cells showed reduced degranulation. The results showed a kind of mechanism that SH-induced anaphylactoid reactions were mediated by MRGPRX2 via activating PLC molecular signaling pathways to provoke mast cells Ca2+ mobilization and degranulation. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:214 / 223
页数:10
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