Purine Release, Metabolism, and Signaling in the Inflammatory Response

Joel Linden, Friedrich Koch-Nolte, Gerhard Dahl

Research output: Contribution to journalReview articlepeer-review

91 Scopus citations


ATP, NAD+, and nucleic acids are abundant purines that, in addition to having critical intracellular functions, have evolved extracellular roles as danger signals released in response to cell lysis, apoptosis, degranulation, or membrane pore formation. In general ATP and NAD+ have excitatory and adenosine has anti-inflammatory effects on immune cells. This review focuses on recent advances in our understanding of purine release mechanisms, ectoenzymes that metabolize purines (CD38, CD39, CD73, ENPP1, and ENPP2/autotaxin), and signaling by key P2 purinergic receptors (P2X7, P2Y2, and P2Y12). In addition to metabolizing ATP or NAD+, some purinergic ectoenzymes metabolize other inflammatory modulators, notably lysophosphatidic acid and cyclic GMP-AMP (cGAMP). Also discussed are extracellular signaling effects of NAD+ mediated by ADP-ribosylation, and epigenetic effects of intracellular adenosine mediated by modification of S-adenosylmethionine-dependent DNA methylation.

Original languageEnglish (US)
Pages (from-to)325-347
Number of pages23
JournalAnnual review of immunology
StatePublished - Apr 26 2019


  • ADP-ribosylation
  • DNA methylation
  • NAD+
  • NLRP3 inflammasome
  • P2X receptors
  • P2Y receptors
  • adenosine receptors
  • autotaxin
  • cGAMP
  • ectonucleotidases
  • lysophosphatidic acid
  • pannexin 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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