Platelet-conditioned media induces an anti-inflammatory macrophage phenotype through EP4.
atherosclerosis
inflammation
macrophages
platelets
prostaglandin E2
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
12
05
2020
revised:
24
10
2020
accepted:
27
10
2020
pubmed:
11
11
2020
medline:
15
5
2021
entrez:
10
11
2020
Statut:
ppublish
Résumé
Platelets are increasingly recognized as immune cells. As such, they are commonly seen to induce and perpetuate inflammation; however, anti-inflammatory activities are increasingly attributed to them. Atherosclerosis is a chronic inflammatory condition. Similar to other inflammatory conditions, the resolution of atherosclerosis requires a shift in macrophages to an M2 phenotype, enhancing their efferocytosis and cholesterol efflux capabilities. To assess the effect of platelets on macrophage phenotype. In several in vitro models employing murine (RAW264.7 and bone marrow-derived macrophages) and human (THP-1 and monocyte-derived macrophages) cells, we exposed macrophages to media in which non-agonized human platelets were cultured for 60 minutes (platelet-conditioned media [PCM]) and assessed the impact on macrophage phenotype and function. Across models, we demonstrated that PCM from healthy humans induced a pro-resolving phenotype in macrophages. This was independent of signal transducer and activator of transcription 6 (STAT6), the prototypical pathway for M2 macrophage polarization. Stimulation of the EP4 receptor on macrophages by prostaglandin E2 present in PCM, is at least partially responsible for altered gene expression and associated function of the macrophages-specifically reduced peroxynitrite production, increased efferocytosis and cholesterol efflux capacity, and increased production of pro-resolving lipid mediators (ie, 15R-LXA Platelet-conditioned media induces an anti-inflammatory, pro-resolving phenotype in macrophages. Our findings suggest that therapies targeting hemostatic properties of platelets, while not influencing pro-resolving, immune-related activities, could be beneficial for the treatment of atherothrombotic disease.
Sections du résumé
BACKGROUND
Platelets are increasingly recognized as immune cells. As such, they are commonly seen to induce and perpetuate inflammation; however, anti-inflammatory activities are increasingly attributed to them. Atherosclerosis is a chronic inflammatory condition. Similar to other inflammatory conditions, the resolution of atherosclerosis requires a shift in macrophages to an M2 phenotype, enhancing their efferocytosis and cholesterol efflux capabilities.
OBJECTIVES
To assess the effect of platelets on macrophage phenotype.
METHODS
In several in vitro models employing murine (RAW264.7 and bone marrow-derived macrophages) and human (THP-1 and monocyte-derived macrophages) cells, we exposed macrophages to media in which non-agonized human platelets were cultured for 60 minutes (platelet-conditioned media [PCM]) and assessed the impact on macrophage phenotype and function.
RESULTS
Across models, we demonstrated that PCM from healthy humans induced a pro-resolving phenotype in macrophages. This was independent of signal transducer and activator of transcription 6 (STAT6), the prototypical pathway for M2 macrophage polarization. Stimulation of the EP4 receptor on macrophages by prostaglandin E2 present in PCM, is at least partially responsible for altered gene expression and associated function of the macrophages-specifically reduced peroxynitrite production, increased efferocytosis and cholesterol efflux capacity, and increased production of pro-resolving lipid mediators (ie, 15R-LXA
CONCLUSIONS
Platelet-conditioned media induces an anti-inflammatory, pro-resolving phenotype in macrophages. Our findings suggest that therapies targeting hemostatic properties of platelets, while not influencing pro-resolving, immune-related activities, could be beneficial for the treatment of atherothrombotic disease.
Identifiants
pubmed: 33171016
doi: 10.1111/jth.15172
pmc: PMC7902474
mid: NIHMS1655795
pii: S1538-7836(22)00656-0
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Culture Media, Conditioned
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
562-573Subventions
Organisme : NHLBI NIH HHS
ID : HL084312
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL144993
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL131481
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL131478
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL131478
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL10673
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL139909
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 14CRP18850107
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL135398
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 18POST34080390
Pays : United States
Organisme : Deutsche Forschungsgemeinschaft
ID : RO 6121/1-1
Organisme : NCATS NIH HHS
ID : UL1 TR001445
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL106173
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL131481
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL136044
Pays : United States
Organisme : NIGMS NIH HHS
ID : P01 GM095467
Pays : United States
Organisme : American Heart Association
ID : 14CRP18850107
Organisme : NHLBI NIH HHS
ID : K23 HL135398
Pays : United States
Organisme : American Heart Association
ID : 18POST34080390
Organisme : NIGMS NIH HHS
ID : GM095467
Pays : United States
Organisme : NCATS NIH HHS
ID : TR001446
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139909
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001446
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL084312
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL144993
Pays : United States
Organisme : NHLBI NIH HHS
ID : F32 HL136044
Pays : United States
Informations de copyright
© 2020 International Society on Thrombosis and Haemostasis.
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