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Updated: Aug 14, 2026
11:31
Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays
Published on: July 4, 2018
Human mast cells express multiple EP receptors for prostaglandin E2 that differentially modulate activation responses
Chunli Feng1, Elizabeth M Beller, Savita Bagga
1Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Blood
|December 17, 2005
Summary
Prostaglandin E2 (PGE2) suppresses allergic responses by acting on human mast cells (hMCs). It activates EP3 receptors, but also inhibits allergic mediator release via EP2 and EP4 receptors, explaining its potent anti-allergic effects.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Prostaglandin E2 (PGE2) exhibits dual effects on mast cells (MCs), inhibiting allergic responses in vivo while activating them in vitro.
- Understanding the specific roles of PGE2's EP receptors on human MCs (hMCs) is crucial for elucidating its immunomodulatory functions.
Purpose of the Study:
- To investigate the functional roles of EP3, EP2, and EP4 receptors for PGE2 on cultured human mast cells (hMCs).
- To determine the signaling pathways involved in PGE2-mediated mast cell activation and suppression of allergic responses.
Main Methods:
- Cultured human mast cells (hMCs) were treated with PGE2 and selective EP receptor agonists.
- Measurements included cyclic adenosine monophosphate (cAMP) accumulation, eicosanoid and prostaglandin D2 (PGD2) production, leukotriene C4 (LTC4) formation, tumor necrosis factor-alpha (TNF-alpha) generation, extracellular signal-regulated kinase (ERK) phosphorylation, exocytosis, and inducible cAMP early repressor (ICER) expression.
- Protein kinase A (PKA) inhibition was used to dissect signaling pathways.
Main Results:
- hMCs expressed EP3, EP2, and EP4 receptors.
- PGE2 stimulated cAMP, suppressed Fc epsilonRI-mediated eicosanoid and TNF-alpha production, and induced ERK phosphorylation, exocytosis, PGD2, and LTC4 production (when PKA was inhibited).
- EP3 receptor activation mimicked PGE2's effects on ERK, exocytosis, and eicosanoid formation, while EP2 and EP4 agonists increased cAMP. PGE2 induced ICER expression via PKA and ERK.
Conclusions:
- PGE2 activates hMCs via EP3 receptors but suppresses Fc epsilonRI-mediated responses through EP2/EP4 receptors and PKA, and blocks cytokine transcription.
- These complex receptor-mediated actions explain PGE2's potent ability to suppress both early- and late-phase allergic reactions.
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