Surface AMP deaminase 2 as a novel regulator modifying extracellular adenine nucleotide metabolism.
RRIDs
adenosine
inflammation
nucleotidases
purines
rheumatoid arthritis
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
06
04
2021
received:
09
12
2020
accepted:
06
05
2021
entrez:
23
6
2021
pubmed:
24
6
2021
medline:
20
7
2021
Statut:
ppublish
Résumé
Adenine nucleotides represent crucial immunomodulators in the extracellular environment. The ectonucleotidases CD39 and CD73 are responsible for the sequential catabolism of ATP to adenosine via AMP, thus promoting an anti-inflammatory milieu induced by the "adenosine halo". AMPD2 intracellularly mediates AMP deamination to IMP, thereby both enhancing the degradation of inflammatory ATP and reducing the formation of anti-inflammatory adenosine. Here, we show that this enzyme is expressed on the surface of human immune cells and its predominance may modify inflammatory states by altering the extracellular milieu. Surface AMPD2 (eAMPD2) expression on monocytes was verified by immunoblot, surface biotinylation, mass spectrometry, and immunofluorescence microscopy. Flow cytometry revealed enhanced monocytic eAMPD2 expression after TLR stimulation. PBMCs from patients with rheumatoid arthritis displayed significantly higher levels of eAMPD2 expression compared with healthy controls. Furthermore, the product of AMPD2-IMP-exerted anti-inflammatory effects, while the levels of extracellular adenosine were not impaired by an increased eAMPD2 expression. In summary, our study identifies eAMPD2 as a novel regulator of the extracellular ATP-adenosine balance adding to the immunomodulatory CD39-CD73 system.
Identifiants
pubmed: 34159634
doi: 10.1096/fj.202002658RR
doi:
Substances chimiques
GPI-Linked Proteins
0
Adenosine Triphosphate
8L70Q75FXE
5'-Nucleotidase
EC 3.1.3.5
NT5E protein, human
EC 3.1.3.5
AMP Deaminase
EC 3.5.4.6
AMPD2 protein, human
EC 3.5.4.6
Apyrase
EC 3.6.1.5
ENTPD1 protein, human
EC 3.6.1.5
Adenine
JAC85A2161
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21684Informations de copyright
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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