A2A adenosine receptor activation prevents neutrophil aging and promotes polarization from N1 towards N2 phenotype

Extracellular adenosine is a biologically active signaling molecule that accumulates at sites of metabolic stress in sepsis. Extracellular adenosine has potent immunosuppressive effects by binding to and activating G protein-coupled A 2A adenosine receptors (A 2A ARs) on the surface of neutrophils....

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Veröffentlicht in:Purinergic signalling 2022-09, Vol.18 (3), p.345-358
Hauptverfasser: Lovászi, Marianna, Németh, Zoltán H., Pacher, Pál, Gause, William C., Wagener, Gebhard, Haskó, György
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container_end_page 358
container_issue 3
container_start_page 345
container_title Purinergic signalling
container_volume 18
creator Lovászi, Marianna
Németh, Zoltán H.
Pacher, Pál
Gause, William C.
Wagener, Gebhard
Haskó, György
description Extracellular adenosine is a biologically active signaling molecule that accumulates at sites of metabolic stress in sepsis. Extracellular adenosine has potent immunosuppressive effects by binding to and activating G protein-coupled A 2A adenosine receptors (A 2A ARs) on the surface of neutrophils. A 2A AR signaling reproduces many of the phenotypic changes in neutrophils that are characteristic of sepsis, including decreased degranulation, impaired chemotaxis, and diminished ability to ingest and kill bacteria. We hypothesized that A 2A ARs also suppress neutrophil aging, which precedes cell death, and N1 to N2 polarization. Using human neutrophils isolated from healthy subjects, we demonstrate that A 2A AR stimulation slows neutrophil aging, suppresses cell death, and promotes the polarization of neutrophils from an N1 to N2 phenotype. Using genetic knockout and pharmacological blockade, we confirmed that A 2A ARs decrease neutrophil aging in murine sepsis induced by cecal ligation and puncture. A 2A ARs expression is increased in neutrophils from septic patients compared to healthy subject but A 2A AR expression fails to correlate with aging or N1/N2 polarization. Our data reveals that A 2A ARs regulate neutrophil aging in healthy but not septic neutrophils.
doi_str_mv 10.1007/s11302-022-09884-0
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Extracellular adenosine has potent immunosuppressive effects by binding to and activating G protein-coupled A 2A adenosine receptors (A 2A ARs) on the surface of neutrophils. A 2A AR signaling reproduces many of the phenotypic changes in neutrophils that are characteristic of sepsis, including decreased degranulation, impaired chemotaxis, and diminished ability to ingest and kill bacteria. We hypothesized that A 2A ARs also suppress neutrophil aging, which precedes cell death, and N1 to N2 polarization. Using human neutrophils isolated from healthy subjects, we demonstrate that A 2A AR stimulation slows neutrophil aging, suppresses cell death, and promotes the polarization of neutrophils from an N1 to N2 phenotype. Using genetic knockout and pharmacological blockade, we confirmed that A 2A ARs decrease neutrophil aging in murine sepsis induced by cecal ligation and puncture. A 2A ARs expression is increased in neutrophils from septic patients compared to healthy subject but A 2A AR expression fails to correlate with aging or N1/N2 polarization. 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subjects Adenosine
Aging
Apoptosis
Biological activity
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cecum
Cell activation
Cell death
Chemotaxis
Degranulation
G protein-coupled receptors
Human Physiology
Leukocytes (neutrophilic)
Neurosciences
Neutrophils
Original
Original Article
Pharmacology/Toxicology
Phenotypes
Polarization
Receptor mechanisms
Sepsis
title A2A adenosine receptor activation prevents neutrophil aging and promotes polarization from N1 towards N2 phenotype
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