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Purine Release, Metabolism, and Signaling in the Inflammatory Response

Authors
  • Linden, Joel
  • Koch-Nolte, Friedrich
  • Dahl, Gerhard
Type
Published Article
Journal
Annual Review of Immunology
Publisher
Annual Reviews
Publication Date
Apr 26, 2019
Volume
37
Pages
325–347
Identifiers
DOI: 10.1146/annurev-immunol-051116-052406
Source
Annual Reviews
Keywords
License
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Abstract

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.

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