Mas-Related G Protein-Coupled Receptor-X2 (MRGPRX2) in Drug Hypersensitivity Reactions

Porębski, Grzegorz; Kwiecień, Kamila; Pawica, Magdalena; Kwitniewski, Mateusz

doi:10.3389/fimmu.2018.03027

Cited by 143 publications

(118 citation statements)

References 64 publications

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…Anaphylaxis is a type-I IgE mediated allergic reaction caused by the activation of mast cells, whereas anaphylactoid reactions or pseudo-allergic reactions are non-immunologic sudden onset reactions mediated through the non-IgE pathway. The clinical symptoms of anaphylactoid shock, however, are similar to anaphylaxis [1]. Activation of mast cells by allergen or drugs causes a profound release of inflammatory mediators, which leads to anaphylactoid shock [2].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2)

et al. 2020

View full text Add to dashboard Cite

Anaphylactoid shock is a fatal hypersensitivity response caused by non-IgE mediated mast cell activation. These reactions are mediated by a family of G protein-coupled receptors (GPCRs) known as Mas related GPCRX2 (MRGPRX2). Several US FDA approved drugs which are used in day to day life have been reported to cause anaphylactoid shock. Surprisingly, no therapeutic drugs are available which can directly target MRGPRX2 for treatment of anaphylactoid shock. Genistein is a non-steroidal polyphenol known for its diverse physiological and pharmacological activities. In recent studies, Genistein has been reported for its anti-inflammatory activity on mast cells. However, the effects and mechanistic pathways of Genistein on anaphylactoid reaction remain unknown. In the present study, we designed a battery of in-vitro, in-silico and in-vivo experiments to evaluate the anti-anaphylactoid activity of Genistein in order to understand the possible molecular mechanisms of its action. The in-vitro results demonstrated the inhibitory activity of Genistein on MRGPRX2 activation. Further, a mouse model of anaphylactoid shock was used to evaluate the inhibitory activity of Genistein on blood vessel leakage and hind paw edema. Taken together, our findings have demonstrated a therapeutic potential of Genistein as a lead compound in the treatment of anaphylactoid shock via MRGPRX2.

show abstract

Section: Introductionmentioning

confidence: 99%

Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2)

et al. 2020

View full text Add to dashboard Cite

show abstract

“…MRGPRX2 is mostly associated with the tryptase/chymase positive MCs (MC TC ) that are predominant in the skin [14,15,27]. MRGPRX2 can be activated by various peptides encompassing drugs, antimicrobial peptides, and neuropeptides like Substance P (SP), making the receptor quite universal [17,19,28]. While thimerosal caused footpad swelling under local injection in wild-type mice, we found that neither mast celldeficient mice nor MrgprB2-knockout mice responded to local thimerosal injection.…”

Section: Discussionmentioning

confidence: 87%

“…MRGPRX2, a member of the Mas-related gene family, was found to be expressed in sensory neurons of dorsal root ganglia, mast cells, and keratinocytes [17]. Its ortholog in mouse is MrgprB2.…”

Section: Introductionmentioning

confidence: 99%

“…MRGPRX2 and MrgprB2 are expressed at high levels in mast cells in human and mouse skin, respectively [13,14]. Previous studies have shown that mouse MrgprB2 and the human MRGPRX2 are activated not only by basic secretagogues and neurokinins [17,18], but also a number of small-molecule drugs (such as antimicrobials, mivacurium) [18,19], producing direct mast cell degranulation and pseudo-allergic reactions. However, whether thimerosal can directly activate mast cells to induce contact dermatitis has not been reported.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thimerosal induces skin pseudo-allergic reaction via Mas-related G-protein coupled receptor B2

Peng

Che

Hao

et al. 2019

Journal of Dermatological Science

View full text Add to dashboard Cite

Background: Thimerosal has been used as a preservative in many products which may cause contact dermatitis. It is the second most common allergen in positive patch test reactions, though being a clinical irrelevant allergen. Thimerosal-induced contact dermatitis is generally considered to be a delayed-type hypersensitivity reaction, but it is difficult to explain the fact that most patients develop an allergic reaction upon first encounter with thimerosal. Recent studies have demonstrated the association between Mas-related G protein coupled receptor X2 (MRGPRX2) and pseudo-allergic reactions which occur at the first contact with stimulation. This suggests the possibility that thimerosal may cause contact dermatitis via MRGPRX2 mediated mechanism. Objectives: To investigate the role of Mas-related G-protein coupled receptor B2 (MrgprB2)/MRGPRX2 in contact dermatitis induced by thimerosal. Methods: Thimerosal induced pseudo-allergic reactions via MrgprB2/ MRGPRX2 were investigated using a novel skin pseudo-allergic reaction mouse model, footpad swelling and extravasation assays in vivo and mast cell degranulation assay in vitro. Results: Thimerosal induced contact dermatitis in dorsal skin and footpad swelling in wild-type mice, but had no significant effect in MrgprB2-knockout mice. Thimerosal-induced dermatitis is characterized by infiltration of inflammatory cells and elevation of serum histamine and inflammatory cytokines, rather than elevation of serum IgE level. Thimerosal increased the intracellular Ca 2+ concentration in HEK293 cells overexpressing MrgprB2/MRGPRX2. Downregulation of MRGPRX2 resulted in the reduced degranulation of LAD2 human mast cells. Conclusions: MrgprB2 mediates thimerosal-induced mast cell degranulation and pseudo-allergic reaction in mice. MRGPRX2 may be a key contributor to human contact dermatitis.

show abstract

“…Leysen et al suggested that quantification of specific IgE [6,7]. In a recent animal study, it was shown that NMBA activates mast cell degranulation through Mas-related G-protein-coupled receptor member X2 (MRGPRX2) activation independent of the presence of IgE antibodies [14,15]. Activation of this receptor induces a non-IgEmediated response in NMBA-naïve patients such as a pseudo-allergic reaction.…”

Section: Discussionmentioning

confidence: 99%

Skin Testing to Identify Safe Drugs for Patients with Rocuronium-Induced Anaphylaxis

Suzuki¹,

Kawase

Ogita

et al. 2020

Case Reports in Anesthesiology

View full text Add to dashboard Cite

Among patients who develop anaphylaxis during anesthesia, anaphylaxis caused by a neuromuscular blocking agent has the highest incidence. In patients who developed IgE-mediated anaphylaxis, and cross-reactivity among NMBAs is a concern in subsequent anesthetic procedures. We present a patient who developed rocuronium-induced anaphylaxis in whom the skin prick test (SPT) and intradermal test (IDT) could identify a safe drug to use in the subsequent anesthetic procedure. A 32-year-old female developed anaphylactic shock at the induction of general anesthesia. She recovered by administration of hydrocortisone and epinephrine. Skin tests including the SPT followed by the IDT revealed rocuronium as the drug that caused anaphylaxis and vecuronium as a safe drug to use for the subsequent general anesthesia. She safely underwent surgery with general anesthesia using vecuronium one month after the skin testing. There are not many reports on the effectiveness of the SPT followed by IDT in identifying the causative drug as well as a safe drug to use in the subsequent anesthetic procedure following anaphylaxis during anesthesia. The usefulness of the SPT should be re-evaluated.

show abstract

Mas-Related G Protein-Coupled Receptor-X2 (MRGPRX2) in Drug Hypersensitivity Reactions

Cited by 143 publications

References 64 publications

Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2)

Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2)

Thimerosal induces skin pseudo-allergic reaction via Mas-related G-protein coupled receptor B2

Skin Testing to Identify Safe Drugs for Patients with Rocuronium-Induced Anaphylaxis

Contact Info

Product

Resources

About