Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
2019
Publication Source
Journal of Immunology
Volume
202
Issue
4
Start Page
1229
Last Page
1238
DOI
10.4049/jimmunol.1801227
Abstract
AG-30/5C is an angiogenic host defense peptide that activates human mast cells (MC) via an unknown mechanism. Using short hairpin RNA–silenced human MC line LAD2 and stably transfected RBL-2H3 cells, we demonstrate that AG-30/5C induces MC degranulation via Mas-related G protein–coupled receptor X2 (MRGPRX2). Most G protein–coupled receptors signal via parallel and independent pathways mediated by G proteins and b-arrestins. AG-30/5C and compound 48/80 induced similar maximal MC degranulation via MRGPRX2, which was abolished by pertussis toxin. However, compound 48/80 induced a robust b-arrestin activation as determined by transcriptional activation following arrestin translocation (Tango), but AG-30/5C did not. Overnight culture of MC with compound 48/80 resulted in reduced cell surface MRGPRX2 expression, and this was associated with a significant decrease in subsequent MC degranulation in response to compound 48/80 or AG-30/5C. However, AG-30/5C pretreatment had no effect on cell surface MRGPRX2 expression or degranulation in response to compound 48/80 or AG-30/5C. Icatibant, a bradykinin B 2 receptor antagonist, promotes MC degranulation via MRGPRX2 and causes pseudoallergic drug reaction. Icatibant caused MC degranulation via a pertussis toxin–sensitive G protein but did not activate b-arrestin. A screen of the National Institutes of Health Clinical Collection library led to the identification of resveratrol as an inhibitor of MRGPRX2. Resveratrol inhibited compound 48/80–induced Tango and MC degranulation in response to compound 48/80, AG-30/5C, and Icatibant. This study demonstrates the novel finding that AG-30/5C and Icatibant serve as G protein–biased agonists for MRGPRX2, but compound 48/80 signals via both G protein and b-arrestin with distinct differences in receptor regulation. Copyright © 2019 by The American Association of Immunologists, Inc. All rights reserved
Keywords
Animals; Bradykinin; Bradykinin B2 Receptor Antagonists; Cells, Cultured; HEK293 Cells; Humans; Mast Cells; Nerve Tissue Proteins; Peptides; Rats; Receptors, G-Protein-Coupled; Receptors, Neuropeptide
Recommended Citation
Roy, S., Ganguly, A., Haque, M., & Ali, H. (2019). Angiogenic Host Defense Peptide Ag-30/5C and Bradykinin B 2 receptor Antagonist Icatibant are G Protein Biased Agonists for MRGPRX2 in Mast Cells. Journal of Immunology, 202 (4), 1229-1238. http://dx.doi.org/10.4049/jimmunol.1801227
Date Posted: 10 February 2023
This document has been peer reviewed.