Mas-related G protein-coupled receptor MRGPRX2 in human basophils: Expression and functional studies

Front Immunol. 2023 Jan 16:13:1026304. doi: 10.3389/fimmu.2022.1026304. eCollection 2022.

Abstract

Background: Occupancy of MRGPRX2 heralds a new era in our understandings of immediate drug hypersensitivity reactions (IDHRs), but a constitutive expression of this receptor by basophils is debated.

Objective: To explore the expression and functionality of MRGPRX2 in and on basophils.

Methods: Basophils from patients with birch pollen allergy, IDHRs to moxifloxacin, and healthy controls were studied in different conditions, that is, in rest, after stimulation with anti-IgE, recombinant major birch pollen allergen (rBet v 1), moxifloxacin, fMLP, substance P (SP), or other potential basophil secretagogues. In a separate set of experiments, basophils were studied after purification and resuspension in different media.

Results: Resting whole blood basophils barely express MRGPRX2 on their surface and are unresponsive to SP or moxifloxacin. However, surface MRGPRX2 is quickly upregulated upon incubation with anti-IgE or fMLP. Pre-stimulation with anti-IgE can induce a synergic effect on basophil degranulation in IgE-responsive subjects after incubation with SP or moxifloxacin, provided that basophils have been obtained from patients who experienced an IDHR to moxifloxacin. Cell purification can trigger a "spontaneous" and functional upregulation of MRGPRX2 on basophils, not seen in whole blood cells, and its surface density can be influenced by distinct culture media.

Conclusion: Basophils barely express MRGPRX2 in resting conditions. However, the receptor can be quickly upregulated after stimulation with anti-IgE, fMLP, or after purification, making cells responsive to MRGPRX2 occupation. We anticipate that such "conditioned" basophils constitute a model to explore MRGPRX2 agonism or antagonism, including IDHRs originating from the occupation of this receptor.

Keywords: CD203c; CD63; MRGPRX2; allergy; basophils; moxifloxacin; substance P..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / metabolism
  • Basophils
  • Drug Hypersensitivity* / metabolism
  • Humans
  • Hypersensitivity, Immediate* / metabolism
  • Immunoglobulin E
  • Moxifloxacin
  • Nerve Tissue Proteins / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Neuropeptide / genetics
  • Receptors, Neuropeptide / metabolism

Substances

  • Immunoglobulin E
  • Moxifloxacin
  • Allergens
  • Receptors, G-Protein-Coupled
  • MRGPRX2 protein, human
  • Nerve Tissue Proteins
  • Receptors, Neuropeptide

Grants and funding

The authors would like to thank ABBVIE (Brussels, BE) and ROCHE (Brussels, BE) for unrestricted grants. DE is a senior clinical researcher of the Research Foundation Flanders/Fonds Wetenschappelijk Onderzoek (FWO: 1800614N). VS is a senior clinical researcher of the Research Foundation Flanders/Fonds Wetenschappelijk Onderzoek (FWO: 1804518N).