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Published on: September 15, 2017
Purine Release, Metabolism, and Signaling in the Inflammatory Response
Joel Linden1,2, Friedrich Koch-Nolte3, Gerhard Dahl4
1Division of Developmental Immunology, La Jolla Institute for Immunology, La Jolla, California 92037, USA;
Extracellular purines like ATP and NAD+ act as danger signals. This review explores their release, metabolism by ectoenzymes, and signaling via purinergic receptors, impacting immune responses.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Purines such as adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+) have crucial intracellular roles.
- Extracellularly, these purines function as danger signals released during cell damage or death.
- Immune cells are modulated by extracellular purines, with ATP and NAD+ generally being excitatory, while adenosine exhibits anti-inflammatory effects.
Purpose of the Study:
- To review recent advancements in understanding extracellular purine signaling.
- To highlight the mechanisms of purine release and the roles of key ectoenzymes in their metabolism.
- To discuss the signaling pathways involving specific purinergic receptors and the broader implications of purine metabolism.
Main Methods:
- Literature review focusing on recent scientific publications.
- Analysis of purine release mechanisms, including cell lysis, apoptosis, degranulation, and pore formation.
- Examination of the enzymatic activity of ectoenzymes (CD38, CD39, CD73, ENPP1, ENPP2/autotaxin) on purines and other inflammatory mediators.
- Review of signaling pathways mediated by purinergic receptors (P2X7, P2Y2, P2Y12).
Main Results:
- Purines are released extracellularly as danger signals, influencing immune cell activity.
- Ectoenzymes play a critical role in metabolizing extracellular purines (ATP, NAD+) and other molecules like lysophosphatidic acid and cyclic GMP-AMP (cGAMP).
- Specific purinergic receptors (P2X7, P2Y2, P2Y12) mediate the signaling effects of these extracellular purines.
- Extracellular NAD+ signaling involves ADP-ribosylation, and intracellular adenosine influences DNA methylation via S-adenosylmethionine.
Conclusions:
- Extracellular purines are key mediators of cellular communication and immune responses.
- The interplay between purine release, ectoenzyme activity, and purinergic receptor signaling is complex and multifaceted.
- Understanding these pathways offers insights into inflammatory processes and potential therapeutic targets.
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