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Purine Release, Metabolism, and Signaling in the Inflammatory Response
- Joel Linden1,2, Friedrich Koch-Nolte3, and Gerhard Dahl4
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View Affiliations Hide AffiliationsAffiliations: 1Division of Developmental Immunology, La Jolla Institute for Immunology, La Jolla, California 92037, USA; email: [email protected] 2Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA 3Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany; email: [email protected] 4Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33136, USA; email: [email protected]
- Vol. 37:325-347 (Volume publication date April 2019) https://doi.org/10.1146/annurev-immunol-051116-052406
- First published as a Review in Advance on January 24, 2019
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Copyright © 2019 by Annual Reviews. All rights reserved
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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