Liu Rui, Che Delu, Zhao Tingting, Pundir Priyanka, Cao Jiao, Lv Yanni, Wang Jue, Ma Pengyu, Fu Jia, Wang Nana, Wang Xiaoyang, Zhang Tao, Dong Xinzhong, He Langchong
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
Biochem Pharmacol. 2017 Dec 15;146:214-223. doi: 10.1016/j.bcp.2017.09.017. Epub 2017 Oct 4.
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 Ca mobilization and degranulation.
肥大细胞是独特的免疫细胞，在宿主防御反应如速发型超敏反应和过敏反应中起哨兵细胞的作用。肥大细胞特异性受体MRGPRX2（Mas相关G蛋白偶联受体X2）触发肥大细胞脱颗粒，这是过敏反应中的关键过程。我们试图更好地理解盐酸青藤碱（SH）诱导的过敏反应。使用体内后爪肿胀和渗出试验以及体外肥大细胞脱颗粒试验研究了SH诱导的与MRGPRX2相关的假过敏反应。MrgprB2基因敲除小鼠表现出SH诱导的炎症效应降低。此外，与MRGPRX2（MrgprB2的直系同源基因）相关的人类肥大细胞被SH以剂量依赖性方式激活；然而，MRGPRX2基因敲低的肥大细胞显示脱颗粒减少。结果表明，SH诱导的类过敏反应是由MRGPRX2通过激活PLC分子信号通路引发肥大细胞钙动员和脱颗粒介导的一种机制。
