Next Article in Journal
The Cycling of Intracellular Calcium Released in Response to Fluid Shear Stress Is Critical for Migration-Associated Actin Reorganization in Eosinophils
Next Article in Special Issue
Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3
Previous Article in Journal
Alteration of Neural Stem Cell Functions in Ataxia and Male Sterility Mice: A Possible Role of β-Tubulin Glutamylation in Neurodegeneration
Previous Article in Special Issue
IL-33 and Superantigenic Activation of Human Lung Mast Cells Induce the Release of Angiogenic and Lymphangiogenic Factors
Open AccessCommunication

MRGPRX2 Activation by Rocuronium: Insights from Studies with Human Skin Mast Cells and Missense Variants

1
Department of Basic and Translational Sciences, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA
2
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 20209, USA
*
Author to whom correspondence should be addressed.
Cells 2021, 10(1), 156; https://doi.org/10.3390/cells10010156
Received: 30 December 2020 / Revised: 12 January 2021 / Accepted: 13 January 2021 / Published: 15 January 2021
Perioperative hypersensitivity (POH) to the neuromuscular blocking drug (NMBD) rocuronium was previously thought to be IgE and mast cell (MC)-mediated. However, the recent seminal observation that rocuronium induces degranulation in murine peritoneal MCs (PMCs) via Mas-related G protein-coupled receptor B2 (MrgprB2) led to the idea that POH to this drug involves the activation of MRGPRX2 (human ortholog of MrgprB2). Furthermore, based on the demonstration that a patient with POH to rocuronium displayed three missense mutations (M196I, L226P and L237P) in MRGPRX2’s transmembrane domains, it was proposed that this hypersensitivity reaction resulted from aberrant activation of this receptor. We found that rocuronium at 20 µg/mL caused degranulation in mouse PMCs via MrgprB2 but required at least 500 µg/mL to induce degranulation in human MCs via MRGPRX2. Furthermore, RBL-2H3 cells transiently expressing M196I, L226P and L237P variants did not display enhanced degranulation in response to rocuronium when compared to the wild-type receptor. These findings provide the first demonstration that rocuronium induces degranulation in human MCs via MRGPRX2. Furthermore, the important differences between MrgprB2 and MRGPRX2 and the inability of rocuronium to induce enhanced response in cells expressing MRGPRX2 variants suggest that the mechanism of its POH is more complex than previously thought. View Full-Text
Keywords: anaphylaxis; mast cells; missense mutation; MrgprB2; MRGPRX2; rocuronium anaphylaxis; mast cells; missense mutation; MrgprB2; MRGPRX2; rocuronium
Show Figures

Figure 1

MDPI and ACS Style

Chompunud Na Ayudhya, C.; Amponnawarat, A.; Roy, S.; Oskeritzian, C.A.; Ali, H. MRGPRX2 Activation by Rocuronium: Insights from Studies with Human Skin Mast Cells and Missense Variants. Cells 2021, 10, 156. https://doi.org/10.3390/cells10010156

AMA Style

Chompunud Na Ayudhya C, Amponnawarat A, Roy S, Oskeritzian CA, Ali H. MRGPRX2 Activation by Rocuronium: Insights from Studies with Human Skin Mast Cells and Missense Variants. Cells. 2021; 10(1):156. https://doi.org/10.3390/cells10010156

Chicago/Turabian Style

Chompunud Na Ayudhya, Chalatip; Amponnawarat, Aetas; Roy, Saptarshi; Oskeritzian, Carole A.; Ali, Hydar. 2021. "MRGPRX2 Activation by Rocuronium: Insights from Studies with Human Skin Mast Cells and Missense Variants" Cells 10, no. 1: 156. https://doi.org/10.3390/cells10010156

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop