Proteinase-Mediated Macrophage Signaling in Psoriatic Arthritis.
PAR2
macrophage
monocyte
serine proteinase
spondyloarthritis
synovial fluid
tryptase-6
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
15
11
2020
accepted:
29
12
2020
entrez:
25
3
2021
pubmed:
26
3
2021
medline:
24
6
2021
Statut:
epublish
Résumé
Multiple proteinases are present in the synovial fluid (SF) of an arthritic joint. We aimed to identify inflammatory cell populations present in psoriatic arthritis (PsA) SF compared to osteoarthritis (OA) and rheumatoid arthritis (RA), identify their proteinase-activated receptor 2 (PAR2) signaling function and characterize potentially active SF serine proteinases that may be PAR2 activators. Flow cytometry was used to characterize SF cells from PsA, RA, OA patients; PsA SF cells were further characterized by single cell 3'-RNA-sequencing. Active serine proteinases were identified through cleavage of fluorogenic trypsin- and chymotrypsin-like substrates, activity-based probe analysis and proteomics. Fluo-4 AM was used to monitor intracellular calcium cell signaling. Cytokine expression was evaluated using a multiplex Luminex panel. PsA SF cells were dominated by monocytes/macrophages, which consisted of three populations representing classical, non-classical and intermediate cells. The classical monocytes/macrophages were reduced in PsA compared to OA/RA, whilst the intermediate population was increased. PAR2 was elevated in OA vs. PsA/RA SF monocytes/macrophages, particularly in the intermediate population. PAR2 expression and signaling in primary PsA monocytes/macrophages significantly impacted the production of monocyte chemoattractant protein-1 (MCP-1). Trypsin-like serine proteinase activity was elevated in PsA and RA SF compared to OA, while chymotrypsin-like activity was elevated in RA compared to PsA. Tryptase-6 was identified as an active serine proteinase in SF that could trigger calcium signaling partially PAR2 and its activating proteinases, including tryptase-6, can be important mediators of inflammation in PsA. Components within this proteinase-receptor axis may represent novel therapeutic targets.
Identifiants
pubmed: 33763056
doi: 10.3389/fimmu.2020.629726
pmc: PMC7982406
doi:
Substances chimiques
F2RL1 protein, human
0
Receptor, PAR-2
0
Tryptases
EC 3.4.21.59
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
629726Subventions
Organisme : CIHR
ID : PJT 148565
Pays : Canada
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2021 Abji, Rasti, Gómez-Aristizábal, Muytjens, Saifeddine, Mihara, Motahhari, Gandhi, Viswanathan, Hollenberg, Oikonomopoulou and Chandran.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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