A Mast-Cell-Specific Receptor Mediates Neurogenic Inflammation and Pain.
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
06 02 2019
06 02 2019
Historique:
received:
21
06
2018
revised:
29
10
2018
accepted:
31
12
2018
pubmed:
29
1
2019
medline:
28
8
2019
entrez:
29
1
2019
Statut:
ppublish
Résumé
Mast cells can be found in close proximity to peripheral nerve endings where, upon activation, they release a broad range of pro-inflammatory cytokines and chemokines. However, the precise mechanism underlying this so-called neurogenic inflammation and associated pain has remained elusive. Here we report that the mast-cell-specific receptor Mrgprb2 mediates inflammatory mechanical and thermal hyperalgesia and is required for recruitment of innate immune cells at the injury site. We also found that the neuropeptide substance P (SP), an endogenous agonist of Mrgprb2, facilitates immune cells' migration via Mrgprb2. Furthermore, SP activation of the human mast cell led to the release of multiple pro-inflammatory cytokines and chemokines via the human homolog MRGPRX2. Surprisingly, the SP-mediated inflammatory responses were independent of its canonical receptor, neurokinin-1 receptor (NK-1R). These results identify Mrgprb2/X2 as an important neuroimmune modulator and a potential target for treating inflammatory pain.
Identifiants
pubmed: 30686732
pii: S0896-6273(19)30013-3
doi: 10.1016/j.neuron.2019.01.012
pmc: PMC6462816
mid: NIHMS1017624
pii:
doi:
Substances chimiques
Cytokines
0
Mrgprb2 protein, mouse
0
Mrgprx2 protein, mouse
0
Receptors, G-Protein-Coupled
0
Receptors, Neurokinin-1
0
Substance P
33507-63-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
412-420.e3Subventions
Organisme : NIGMS NIH HHS
ID : F32 GM121030
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI135186
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS054791
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS070201
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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