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

Marianna Lovászi, Zoltán H. Németh, Pál Pacher, William C. Gause, Gebhard Wagener, György Haskó

Research output: Contribution to journalArticlepeer-review

Abstract

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 A2A adenosine receptors (A2AARs) on the surface of neutrophils. A2AAR 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 A2AARs also suppress neutrophil aging, which precedes cell death, and N1 to N2 polarization. Using human neutrophils isolated from healthy subjects, we demonstrate that A2AAR 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 A2AARs decrease neutrophil aging in murine sepsis induced by cecal ligation and puncture. A2AARs expression is increased in neutrophils from septic patients compared to healthy subject but A2AAR expression fails to correlate with aging or N1/N2 polarization. Our data reveals that A2AARs regulate neutrophil aging in healthy but not septic neutrophils.

Original languageEnglish (US)
Pages (from-to)345-358
Number of pages14
JournalPurinergic Signalling
Volume18
Issue number3
DOIs
StatePublished - Sep 2022

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Keywords

  • Adenosine A receptor
  • Neutrophil aging
  • Neutrophil polarization
  • Sepsis

Fingerprint

Dive into the research topics of 'A2A adenosine receptor activation prevents neutrophil aging and promotes polarization from N1 towards N2 phenotype'. Together they form a unique fingerprint.

Cite this