Asthma, Allergy and Immunology

Biography

Biography: Jue Wang

Abstract

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. In 2014, McNeil, et al. reported that MRGPRX2 was crucial for drug-induced pseudoallergic reactions. It is widely observed that antimicrobials, opioid receptor and muscle relaxant agonists can induce pseudo-allergic reactions (i.e. IgE-independent mechanism) with symptoms ranging from skin inflammation to life-threatening systemic anaphylaxis. But the allergy effects of these drugs and the possible mechanisms underlying anaphylactoid reactions have not been demonstrated.

Several drugs were screened by Ca2+ imaging using MRGPRX2 overexpressing HEK293 cells. MRGPRX2 related anaphylactoid reactions induced by these components were investigated using skin swelling and extravasation assays in vivo and mast cell degranulation assay in vitro. We showed that MRGPRX2 is involved in allergic-like reactions to three types of antimicrobials(antifungal agents, aminoglycosides and sulfonamides) and muscle relaxant agonists (Mivacurium and Cisatracurium). These drugs caused pseudo-allergic reactions in wild-type mice by inducing mast cells to release histamine. However, it did not induce a similar phenomenon in Kit^W-sh/W-sh mice. Furthermore, MrgprB2-knockout(MrgprB2 is the murine homologue of MRGPRX2) mice displayed no inflammatory response to them. They induced LAD2 cell degranulation in a dose-dependent manner. They stimulated intracellular calcium ion (Ca²⁺) influx in MRGPRX2-HEK293 cells but not in NC-HEK293 cells. The results of this study suggest that many clinicians should pay more attention to the possible pseudo-allergic reactions caused by these drugs and reduce the risk of allergic reactions.