Background And Objectives: Mast cell (MC) degranulation via activation of the Mas-related G protein-coupled receptor X2 (MRGPRX2) plays a key role in immediate drug hypersensitivity (IDH). However, data in humans are limited to observations in specific cell lines. Objective: To study the usefulness of silencing MRGPRX2 in human MCs with the aim of further unveiling the MRGPRX2 pathway in IDH.
Methods: MCs were cultured from CD34+ progenitor cells obtained from peripheral blood (PBCMCs) and incubated with substance P (as a positive control), rocuronium, moxifloxacin, morphine, or amoxicillin. Immunophenotyping of the cells included flow cytometry and microscopy analyses of the expression of CD117, CD203c, and MRGPRX2. Intracellular calcium was measured using Fluo-4. Degranulation was analyzed by quantifying CD63 expression. For MRGPRX2 silencing, MCs were electroporated with Dicer small interference RNAs.
Results: Incubation of MCs with substance P, morphine, and moxifloxacin increased intracellular calcium levels and triggered MC degranulation, which, for the drugs, is almost completely abolished by selective MRGPRX2 silencing. Despite an increase in intracellular calcium in MRGPRX2+ cells, incubation with nontoxic concentrations of rocuronium does not result in degranulation of PBCMCs. Amoxicillin has no effect on PBCMCs.
Conclusion: The use of MRGPRX2 silencing in human MCs can provide important insights into the role of MRGPRX2 in the pathogenesis of IDH. As induction of calcium signals does not necessarily translate into a secretory response, measurement of the degranulation reaction seems more meaningful in the context of drug testing.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.18176/jiaci.0557 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Understanding retinal tau pathology through functional 2D and 3D iPSC-derived in vitro retinal models.
Acta Neuropathol Commun
January 2025
Department of Physiology and Pharmacology, Sapienza University of Rome, 00185, Rome, Italy.
The generation of retinal models from human induced pluripotent stem cells holds significant potential for advancing our understanding of retinal development, neurodegeneration, and the in vitro modeling of neurodegenerative disorders. The retina, as an accessible part of the central nervous system, offers a unique window into these processes, making it invaluable for both study and early diagnosis. This study investigates the impact of the Frontotemporal Dementia-linked IVS 10 + 16 MAPT mutation on retinal development and function using 2D and 3D retinal models derived from human induced pluripotent stem cells.
View Article and Find Full Text PDFExosomal miR-122 derived from M2 macrophages induces osteogenic differentiation of bone marrow mesenchymal stem cells in the treatment of alcoholic osteonecrosis of the femoral head.
J Orthop Surg Res
January 2025
Department of Joint Osteopathy, Liuzhou Worker's Hospital, Liuzhou, Guangxi Province, 545000, China.
Alcoholic osteonecrosis of the femoral head (AIONFH) is caused by long-term heavy drinking, which leads to abnormal alcohol and lipid metabolism, resulting in femoral head tissue damage, and then pathological necrosis of femoral head tissue. If not treated in time in clinical practice, it will seriously affect the quality of life of patients and even require hip replacement to treat alcoholic femoral head necrosis. This study will confirm whether M2 macrophage exosome (M2-Exo) miR-122 mediates alcohol-induced BMSCs osteogenic differentiation, ultimately leading to the inhibition of femoral head necrosis.
View Article and Find Full Text PDFWireless Stimulation of Barium Titanate@PEDOT Nanoparticles Toward Bioelectrical Modulation in Cancer.
ACS Appl Mater Interfaces
January 2025
Department of Bioengineering and iBB - Institute of Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisbon 1049-001, Portugal.
Cancer cells possess distinct bioelectrical properties, yet therapies leveraging these characteristics remain underexplored. Herein, we introduce an innovative nanobioelectronic system combining a piezoelectric barium titanate nanoparticle core with a conducting poly(3,4-ethylenedioxythiophene) shell (BTO@PEDOT NPs), designed to modulate cancer cell bioelectricity through noninvasive, wireless stimulation. Our hypothesis is that acting as nanoantennas, BTO@PEDOT NPs convert mechanical inputs provided by ultrasound (US) into electrical signals, capable of interfering with the bioelectronic circuitry of two human breast cancer cell lines, MCF-7 and MDA-MB-231.
View Article and Find Full Text PDFMetabolically stable apelin analogs: development and functional role in water balance and cardiovascular function.
Clin Sci (Lond)
January 2025
Center for Interdisciplinary Research in Biology, College de France, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Apelin, a (neuro) vasoactive peptide, plays a prominent role in controlling water balance and cardiovascular functions. Apelin and its receptor co-localize with vasopressin in magnocellular vasopressinergic neurons. Apelin receptors (Apelin-Rs) are also expressed in the collecting ducts of the kidney, where vasopressin type 2 receptors are also present.
View Article and Find Full Text PDFExpression and function of Connexin 43 and Connexin 37 in the murine zona glomerulosa.
Physiol Rep
February 2025
Berlin Institute of Health at Charité, Universitätsmedizin Berlin, Center of Functional Genomics, Berlin, Germany.
The zona glomerulosa (ZG) synthesizes the mineralocorticoid aldosterone. The primary role of aldosterone is the maintenance of volume and electrolyte homeostasis. Aldosterone synthesis is primarily regulated via tightly controlled oscillations in intracellular calcium levels in response to stimulation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!