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Updated: Feb 23, 2026

Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays
Published on: July 4, 2018
Allergic FcεRI- and pseudo-allergic MRGPRX2-triggered mast cell activation routes are independent and inversely
1Department of Dermatology and Allergy, Allergy Center Charité, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Abstract:
While allergic mast cell (MC) degranulation occurs by FcεRI aggregation and varies in strength among subjects, the analogous pseudo-allergic route was recently uncovered to proceed via MRGPRX2. Here, we examine interindividual variability in skin MC responses to FcεRI triggering vs those evoked by MRGPRX2. While population-based variability is comparable between the routes, FcεRI- and MRGPRX2-stimulated pathways are completely independent from each other, and responsiveness to one has therefore no predictive value for the other. Conversely, degranulation triggered by compound 48/80 is highly correlated to the process elicited by substance P. MRGPRX2 mRNA shows pronounced population-based variability (coefficient of variation 102.9%). Surprisingly, stem cell factor (SCF) as the MC-supportive mediator par excellence potently inhibits pseudo-allergic degranulation, while it simultaneously promotes allergic stimulation via FcεRI. We conclude that SCF can have selective MC-dampening functions. Clinically, the data imply that subjects highly reactive in one pathway are not automatically hyper-responsive in terms of the alternative route.
Insights
Allergic and pseudo-allergic mast cell (MC) degranulation pathways are independent, with no predictive value between them. Stem cell factor selectively dampens pseudo-allergic responses while promoting allergic ones.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Mast cells (MCs) mediate allergic reactions via FcεRI aggregation.
- A pseudo-allergic pathway involving MRGPRX2 has been identified.
- Interindividual variability exists in MC responses.
Purpose of the Study:
- To investigate interindividual variability in skin MC degranulation.
- To compare FcεRI-mediated allergic and MRGPRX2-mediated pseudo-allergic pathways.
- To explore the role of stem cell factor (SCF) in these pathways.
Main Methods:
- Examined skin MC responses to FcεRI and MRGPRX2 stimulation.
- Assessed degranulation triggered by compound 48/80 and substance P.
- Quantified MRGPRX2 mRNA expression variability.
- Investigated the effect of SCF on both pathways.
Main Results:
- FcεRI and MRGPRX2 pathways are independent, with no cross-predictive value.
- Degranulation by compound 48/80 correlates with substance P-induced degranulation.
- MRGPRX2 mRNA exhibits significant population-based variability.
- SCF inhibits pseudo-allergic degranulation but promotes FcεRI-mediated degranulation.
Conclusions:
- SCF exhibits selective MC-dampening functions.
- Individual reactivity in one MC degranulation pathway does not predict reactivity in the other.
- Understanding these distinct pathways is crucial for managing allergic and pseudo-allergic conditions.
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