Evidence map›Paper›PMID 23698749›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2013

β-Defensins activate human mast cells via Mas-related gene X2.

Hariharan Subramanian, Kshitij Gupta, Donguk Lee, Arzu K Bayir, Harry Ahn, Hydar Ali

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

70 citing papers in PubMed, 144 citations in OpenAlex.

  1. Article
  2. MRGPRX2 as a novel therapeutic target in headache.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  3. Article
  4. Mutations ofThe journal of allergy and clinical immunology. Global · 2025
    Review
  5. MRGPRX2 Mediates Mast Cell-Induced Endometriosis Pain Through the Sensitization of Sensory Neurons via Histamine/HRH1/TRPV1 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  6. Article
  7. Antimicrobial Peptide Signaling in Skin Diseases.JID innovations : skin science from molecules to population health · 2025
    Review
  8. Mast cell activators as adjuvants for intranasal mucosal vaccines.International journal of pharmaceutics · 2025
    Review
  9. Beyond the classic players: Mas-related G protein-coupled receptor member X2 role in pruritus and skin diseases.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Hariharan SubramanianDepartment of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104-6030, USA.
Kshitij Gupta
Donguk Lee
Arzu K Bayir
Harry Ahn
Hydar Ali
University of Pennsylvania · US

Funding

G Protein Coupled Receptor Signaling in Mast CellsR01HL085774 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ALI, HYDAR · 2008 to 2011
$1.6M
NHLBI NIH HHS R01 HL085774NHLBI NIH HHS R01-HL085774
6 · The paper itself

Abstract

Human β-defensins (hBDs) stimulate degranulation in rat peritoneal mast cells in vitro and cause increased vascular permeability in rats in vivo. In this study, we sought to determine whether hBDs activate murine and human mast cells and to delineate the mechanisms of their regulation. hBD2 and hBD3 did not induce degranulation in murine peritoneal or bone marrow-derived mast cells (BMMC) in vitro and had no effect on vascular permeability in vivo. By contrast, these peptides induced sustained Ca(2+) mobilization and substantial degranulation in human mast cells, with hBD3 being more potent. Pertussis toxin (PTx) had no effect on hBD-induced Ca(2+) mobilization, but La(3+) and 2-aminoethoxydiphenyl borate (a dual inhibitor of inositol 1,4,5-triphosphate receptor and transient receptor potential channels) caused substantial inhibition of this response. Interestingly, degranulation induced by hBDs was substantially inhibited by PTx, La(3+), or 2-aminoethoxydiphenyl borate. Whereas human mast cells endogenously express G protein-coupled receptor, Mas-related gene X2 (MrgX2), rat basophilic leukemia, RBL-2H3 cells, and murine BMMCs do not. Silencing the expression of MrgX2 in human mast cells inhibited hBD-induced degranulation, but had no effect on anaphylatoxin C3a-induced response. Furthermore, ectopic expression of MrgX2 in RBL-2H3 and murine BMMCs rendered these cells responsive to hBDs for degranulation. This study demonstrates that hBDs activate human mast cells via MrgX2, which couples to both PTx-sensitive and insensitive signaling pathways most likely involving Gαq and Gαi to induce degranulation. Furthermore, murine mast cells are resistant to hBDs for degranulation, and this reflects the absence of MrgX2 in these cells.

Indexed as

Animalsbeta-DefensinsCalcium SignalingCell DegranulationCell LineCells, CulturedGene Knockdown TechniquesHumansMast CellsMiceMice, Inbred C57BLMice, TransgenicNerve Tissue ProteinsRatsReceptors, G-Protein-CoupledReceptors, Neuropeptidebeta-DefensinsDEFB103A protein, humanDEFB4A protein, humanMRGPRX2 protein, humanNerve Tissue ProteinsReceptors, G-Protein-CoupledReceptors, Neuropeptide

Identifiers

PMID23698749
PMCPMC3691353
OpenAlexW2100757511

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.