九肽激活肥大细胞致类过敏反应的作用及其机制

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.