九肽激活肥大细胞致类过敏反应的作用及其机制
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篇名: | 九肽激活肥大细胞致类过敏反应的作用及其机制 |
TITLE: | Effects and mechanism of anaphylactoid reaction induced by nonapeptide activating mast cells |
摘要: | 目的 探讨九肽IVQKIKHCF激活肥大细胞引发类过敏反应的作用及潜在机制。方法以人肥大细胞系LAD2为对象,以P物质为阳性对照,通过检测β-氨基己糖苷酶释放率、组胺释放量、炎症因子释放量来考察25、50、100μmol/LIVQKIKHCF的激活作用;分别以敲低MrgprX2的LAD2细胞和Mas相关G蛋白偶联受体X2(MRGPRX2)高表达的人胚胎肾细胞系HEK293(MRGPRX2/HEK293细胞)为对象,通过检测β-氨基己糖苷酶释放率和细胞内钙离子浓度来评价IVQKIKHCF激活作用与MRGPRX2的相关性。结果25、50、100μmol/L的IVQKIKHCF可显著提高LAD2细胞的β-氨基己糖苷酶释放率和组胺释放量(P<0.05),并不同程度地促进肿瘤坏死因子α、白细胞介素8、巨噬细胞炎症蛋白1β、单核细胞趋化蛋白1的释放(P<0.05);敲低MrgprX2后,25、50、100μmol/L的IVQKIKHCF对LAD2细胞β-氨基己糖苷酶释放的促进作用被显著逆转(P<0.05),且可升高MRGPRX2/HEK293细胞内的钙离子浓度。结论九肽IVQKIKHCF可通过激活MRGPRX2而促进肥大细胞释放颗粒物质和炎症介质,从而引发类过敏反应。 |
ABSTRACT: | OBJECTIVE To study the effects and potential mechanism of anaphylactoid reaction induced by nonapeptide IVQKIKHCF activating mast cells. METHODS Using human mast cell line LAD2 as subject, and substance P as positive control, the activation effects of 25, 50 and 100 μmol/L IVQKIKHCF on mast cells were investigated by determining the release rate of β-aminohexosidase, histamine release, and the contents of inflammatory factors; using MrgprX2-knockdown LAD2 cells and Mas- related G protein-coupled receptor X2 (MRGPRX2) high-expression human embryonic kidney cell line HEK293 (MRGPRX2/ HEK293 cells) as subject, the correlation between the activation effect of IVQKIKHCF and MRGPRX2 was investigated by determining the release rate of β-aminohexosidase, and intracellular calcium ion concentration. RESULTS IVQKIKHCF with 25, 50, 100 μmol/L could significantly increase the release rate of β-aminohexosidase and histamine release in LAD2 cells (P<0.05), and promote the release of tumor necrosis factor-α, interleukin-8, macrophage inflammatory protein-1β and monocyte chemotactic protein-1 to varying degrees (P<0.05). After knocking down MrgprX2, the effects of 25, 50, 100 μmol/L IVQKIKHCF promoting the release of β-aminohexosidase in LAD2 cells were reversed significantly (P<0.05), resulting in an increase of calcium ion concentration in MRGPRX2/HEK293 cells. CONCLUSIONS Nonapeptide IVQKIKHCF can promote mast cells to release granular matter and inflammatory mediators by activating MRGPRX2 thus inducing anaphylactoid reaction. |
期刊: | 2023年第34卷第24期 |
作者: | 陈晓敏;刘娜;张丽娜;李友佳 |
AUTHORS: | CHEN Xiaomin,LIU Na,ZHANG Lina,LI Youjia |
关键字: | 九肽;IVQKIKHCF;肥大细胞;类过敏反应;Mas相关G蛋白偶联受体X2 |
KEYWORDS: | nonapeptide; IVQKIKHCF; mast cell; anaphylactoid reaction; Mas-related G protein-coupled receptor X2 |
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