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Mast cell-mediated hypersensitivity to fluoroquinolone is MRGPRX2 dependent.

Authors :
Liu, Rui
Hu, Shiling
Zhang, Yongjing
Che, Delu
Cao, Jiao
Wang, Jue
Zhao, Tingting
Jia, Qianqian
Wang, Nan
Zhang, Tao
Source :
International Immunopharmacology. May2019, Vol. 70, p417-427. 11p.
Publication Year :
2019

Abstract

Abstract Fluoroquinolones trigger anaphylaxis during clinical applications, affecting the safety of their administration. Mast cells are immune cells that act as sentinels during host defenses, mediating hypersensitivity and anaphylactic reactions. Mas-related G protein-coupled receptor X2 (MRGPRX2) is a mast cell-specific receptor that mediates cell degranulation in anaphylactic reactions. In this study, the mechanism underpinning the anaphylactic reactions caused by fluoroquinolones was investigated. Hypersensitivity was assessed through hindpaw swelling, tissue fluid leakage assays, in vivo and body temperature measurements assay in vivo, and cell calcium mobilization assays, and mast cell degranulation assays in vitro. Mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh mice and MrgprB2 (the orthologous receptor of MRGPRX2 in mice) knockout mice exhibited reduced fluoroquinolone-induced anaphylactic effects. Fluoroquinolones activated mast cells in a dose-dependent manner and reduced degranulation was observed following MRGPRX2 silencing. These results reveal that fluoroquinolone-induced anaphylactic reactions are mediated by mast cells through MRGPRX2. Graphical abstract Unlabelled Image Highlights • The mechanism underpinning the anaphylactic reactions caused by fluoroquinolones is proposed. • Mast cell-deficient KitW-sh/W-sh mice and MrgprB2 knockout mice exhibited reduced anaphylactic effects compared with WT mice. • Fluoroquinolones activated mast cells dose-dependently and reduced degranulation was observed following MRGPRX2 silencing. • The mechanism relies on fluoroquinolones-triggered mast cells activation via MRGPRX2. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15675769
Volume :
70
Database :
Academic Search Index
Journal :
International Immunopharmacology
Publication Type :
Academic Journal
Accession number :
135600169
Full Text :
https://doi.org/10.1016/j.intimp.2019.02.001