Mas-related G protein-coupled receptor MRGPRX2 in human basophils: Expression and functional studies.
CD203c
CD63
MRGPRX2
allergy
basophils
moxifloxacin
substance P.
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
23
08
2022
accepted:
30
12
2022
entrez:
2
2
2023
pubmed:
3
2
2023
medline:
4
2
2023
Statut:
epublish
Résumé
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. To explore the expression and functionality of MRGPRX2 in and on basophils. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 36726977
doi: 10.3389/fimmu.2022.1026304
pmc: PMC9885256
doi:
Substances chimiques
Immunoglobulin E
37341-29-0
Moxifloxacin
U188XYD42P
Allergens
0
Receptors, G-Protein-Coupled
0
MRGPRX2 protein, human
0
Nerve Tissue Proteins
0
Receptors, Neuropeptide
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1026304Informations de copyright
Copyright © 2023 Toscano, Elst, Van Gasse, Beyens, van der Poorten, Bridts, Mertens, Van Houdt, Hagendorens, Van Remoortel, Timmermans, Ebo and Sabato.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Int Immunopharmacol. 2022 Jan;102:108389
pubmed: 34920312
Int J Mol Sci. 2019 Oct 23;20(21):
pubmed: 31652731
Cells. 2022 Mar 10;11(6):
pubmed: 35326404
J Allergy Clin Immunol. 2017 Dec;140(6):1726-1728
pubmed: 28689793
J Investig Allergol Clin Immunol. 2021 Dec 21;31(6):489-499
pubmed: 32732181
Allergy. 2017 Dec;72(12):2039-2043
pubmed: 28658502
Nat Chem Biol. 2017 May;13(5):529-536
pubmed: 28288109
J Pharmacol Sci. 2013;122(3):205-12
pubmed: 23803533
J Allergy Clin Immunol. 2014 Sep;134(3):622-633.e9
pubmed: 24954276
Itch (Phila). 2017 Mar;2(1):
pubmed: 28367504
J Allergy Clin Immunol Pract. 2017 Nov - Dec;5(6):1806
pubmed: 29122168
Eur J Immunol. 1991 Feb;21(2):361-8
pubmed: 1705512
Nature. 2015 Mar 12;519(7542):237-41
pubmed: 25517090
Mol Pharmacol. 2011 Jun;79(6):1005-13
pubmed: 21441599
Clin Exp Allergy. 2022 Jun;52(6):797-800
pubmed: 35152504
Front Cell Neurosci. 2019 Jul 03;13:299
pubmed: 31333418
Front Immunol. 2021 Jul 27;12:668962
pubmed: 34385999
Biol Pharm Bull. 2013;36(1):31-5
pubmed: 23302634
Eur J Pharmacol. 2011 Oct 1;668(1-2):299-304
pubmed: 21741965
Clin Exp Allergy. 2022 Nov;52(11):1311-1320
pubmed: 35305051
Cytometry B Clin Cytom. 2008 Jul;74(4):201-10
pubmed: 18412216
J Allergy Clin Immunol Pract. 2019 Mar;7(3):998-1003
pubmed: 30315997
Allergy. 2022 Jun;77(6):1906-1909
pubmed: 35246987
Eur J Immunol. 1991 Apr;21(4):881-5
pubmed: 1708341
J Immunol Methods. 2021 May;492:113003
pubmed: 33647250
Int Arch Allergy Immunol. 2005 Mar;136(3):230-8
pubmed: 15713985
Br J Anaesth. 2020 Dec;125(6):e448-e450
pubmed: 33010928
Cytometry B Clin Cytom. 2013 Mar;84(2):65-70
pubmed: 23355309
J Allergy Clin Immunol Pract. 2015 May-Jun;3(3):396-9
pubmed: 25956313
J Clin Invest. 2016 Oct 3;126(10):3981-3998
pubmed: 27643442
J Invest Dermatol. 2021 Mar;141(3):678-681.e2
pubmed: 32771471
Cytometry B Clin Cytom. 2017 Sep;92(5):348-354
pubmed: 27401129
Allergy. 2014 Oct;69(10):1324-32
pubmed: 24961660
Int Immunopharmacol. 2019 May;70:417-427
pubmed: 30856392
Clin Exp Allergy. 2021 Nov;51(11):1482-1500
pubmed: 34233046
J Immunol Methods. 2021 Aug;495:113061
pubmed: 33933470
J Leukoc Biol. 2001 Aug;70(2):207-18
pubmed: 11493612
Biochim Biophys Acta Gen Subj. 2017 Nov;1861(11 Pt A):2530-2534
pubmed: 28844982
Blood. 2014 Apr 24;123(17):e58-67
pubmed: 24671954
Allergy. 2020 Sep;75(9):2229-2242
pubmed: 32003863
Eur J Immunol. 2017 Nov;47(11):1949-1958
pubmed: 28688196
Front Immunol. 2018 Dec 20;9:3027
pubmed: 30619367
J Allergy Clin Immunol. 2016 Sep;138(3):700-710
pubmed: 27448446
Exp Dermatol. 2010 Sep;19(9):845-7
pubmed: 20545757
JCI Insight. 2016 Oct 06;1(16):e89362
pubmed: 27734033
Gene. 2005 Jun 6;352:30-5
pubmed: 15862286
PLoS One. 2007 Sep 19;2(9):e898
pubmed: 17878933