A

Autor: Marianna, Lovászi, Zoltán H, Németh, Pál, Pacher, William C, Gause, Gebhard, Wagener, György, Haskó
Rok vydání: 2022
Předmět:
Zdroj: Purinergic Signal
ISSN: 1573-9546
Popis: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11302-022-09884-0.
Databáze: OpenAIRE
Externí odkaz: