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Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation
Abstract
Human health is under constant threat of a wide variety of dangers, both self and nonself. The immune system is occupied with protecting the host against such dangers in order to preserve human health. For that purpose, the immune system is equipped with a diverse array of both cellular and non-cellular effectors that are in continuous communication with each other. The naturally occurring nucleotide adenosine 5'-triphosphate (ATP) and its metabolite adenosine (Ado) probably constitute an intrinsic part of this extensive immunological network through purinergic signaling by their cognate receptors, which are widely expressed throughout the body. This review provides a thorough overview of the effects of ATP and Ado on major immune cell types. The overwhelming evidence indicates that ATP and Ado are important endogenous signaling molecules in immunity and inflammation. Although the role of ATP and Ado during the course of inflammatory and immune responses in vivo appears to be extremely complex, we propose that their immunological role is both interdependent and multifaceted, meaning that the nature of their effects may shift from immunostimulatory to immunoregulatory or vice versa depending on extracellular concentrations as well as on expression patterns of purinergic receptors and ecto-enzymes. Purinergic signaling thus contributes to the fine-tuning of inflammatory and immune responses in such a way that the danger to the host is eliminated efficiently with minimal damage to healthy tissues.
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“Prototypical DAMPs derived from necrotic cells include the chromatin-associated protein high-mobility group box 1 (HMGb1)10, heat shock proteins (HSPs)11, and purine metabolites, such as ATP12 and uric acid13 (TABLE 1).”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [12]
Citations
Cites
1 retracted
Budagian, V., Bulanova, E., Brovko, L., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m206383200 · Cited by 107
RetractedImmunobiology of Dendritic Cells
Banchereau, J., Brière, F., Caux, C., Davoust, J. M., Lebecque, S., Liu, Y., Pulendran, B., & Palucka, K. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.767 · Cited by 6,755
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
Tolerance, Danger, and the Extended Family
Matzinger, P. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.005015 · Cited by 4,848
NITRIC OXIDE AND MACROPHAGE FUNCTION
MacMicking, J. D., Xie, Q. W., & Nathan, C. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.323 · Cited by 4,245
The Danger Model: A Renewed Sense of Self
Matzinger, P. (2002) · Science · doi:10.1126/science.1071059 · Cited by 4,205
Receptors for Purines and Pyrimidines
Burnstock, G., & Verkhratsky, A. (2012) · Springer eBooks · doi:10.1007/978-3-642-28863-0_5 · Cited by 3,962
Molecular Physiology of P2X Receptors
North, R. A. (2002) · Physiological Reviews · doi:10.1152/physrev.00015.2002 · Cited by 2,919
Mechanisms of phagocytosis in macrophages
Aderem, A., & Underhill, D. M. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.593 · Cited by 2,854
Points of control in inflammation
Nathan, C. (2002) · Nature · doi:10.1038/nature01320 · Cited by 2,738
Flagged first, then by citations
Research works printed but not linked: 16
- Bowlin, 1995, Inhibition of NF-kappaB nuclear translocation and TNF-alfa gene expression by a novel adenosine A3 receptor agonist, Arthritis Rheum, 38, 1485
- Firestein, 1996, Anti-inflammatory effects of adenosine kinase inhibitors in acute and chronic inflammation, Drug Dev Res, 39, 371, 10.1002/(SICI)1098-2299(199611/12)39:3/4<371::AID-DDR18>3.0.CO;2-4 · DOI
- Fisette, 1996, Modulation of macrophage function by P2Y-purinergic receptors, Drug Dev Res, 39, 377, 10.1002/(SICI)1098-2299(199611/12)39:3/4<377::AID-DDR19>3.0.CO;2-Z · DOI
- Heath, 2003, Dangerous liaisons, Nat Immunol, 425, 460
- Huffnagle, 1997, Mechanisms of macrophage recruitment into infected lungs, Vol. 102, 373
- Jacobson, 1994, Characterization of the adenosine receptor subtype which mediates inhibition of TNF-alfa production in stimulated human monocytes, Drug Dev Res, 31, 282
- Khoa, 2003, Th1 cytokines regulate adenosine receptors and their downstream signaling elements in human microvascular endothelial cells, J Immunol, 171, 3991, 10.4049/jimmunol.171.8.3991 · DOI
- Moore, 2001, Expression pattern of human P2Y receptor subtypes: a quantative reverse transcription-polymerase chain reaction study, Biochim Biophys Acta, 1521, 107, 10.1016/S0167-4781(01)00291-3 · DOI
- Moore, 2003, GPR105, a novel Gi/o-coupled UDP-glucose receptor expressed on brain microglia and peripheral immune cells, is regulated by immunological challenge: possible role in neuroimmune function, Mol Brain Res, 118, 10, 10.1016/S0169-328X(03)00330-9 · DOI
- Murphree, 2003, Lipopolysaccharide (LPS) induces the expression of A2a adenosine receptors in murine WEHI-3 macrophage-like cells, J Leukoc Biol Suppl, 26
- Peters-Golden, 1997, Lipid mediator synthesis by lung macrophages, vol. 102, 151
- Shanley, 1998, Adenosine receptor agonists inhibit macrophage inflammatory protein (MIP)-1alfa production in immunostimulated macrophages, FASEB J, 12, A766
- Szabo, 1998, Adenosine 3 receptor stimulation exerts potent anti-inflammatory effects in vivo, FASEB J, 12, A243
- Varani, 1998, Adenosine A2a receptors of human circulating blood elements, Drug Dev Res, 45, 253, 10.1002/(SICI)1098-2299(199811/12)45:3/4<253::AID-DDR23>3.0.CO;2-Q · DOI
- Zahler, 1998, Adhesion of neutrophils to cultured human endothelial cells is enhanced by stimulation of adenosine A1-receptors, Drug Dev Res, 45, 350, 10.1002/(SICI)1098-2299(199811/12)45:3/4<350::AID-DDR35>3.0.CO;2-L · DOI
- Zimmermann, 1996, Extracellular purine metabolism, Drug Dev Res, 39, 337, 10.1002/(SICI)1098-2299(199611/12)39:3/4<337::AID-DDR15>3.0.CO;2-Z · DOI
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“Extracellular adenosine can inhibit the production of reactive nitrogen species and reactive oxygen species by monocytes/macrophages and neutrophils (Bours et al. 2006; Flamand et al. 2000).”
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Metadata
- Authors
- Bours, M. J. L., Swennen, E. L. R., Di Virgilio, F., Cronstein, B. N., & Dagnelie, P. C.
- Affiliations
- Maastricht University (NL)
- New York University (US)
- Corresponding author
- Bours, M.J.L.
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 112
- Issue
- 2
- Pages
- 358-404
- ISSN
- 0163-7258 (ISSN-L)
- OpenAlex
- W2042906495
- Cited by
- 1,030
- References
- 744
- Citations by year
- 2026: 23 · 2025: 21 · 2024: 33 · 2023: 43 · 2022: 47 · 2021: 47 · 2020: 50 · 2019: 51 · 2018: 56 · 2017: 64 · 2016: 53 · 2015: 57 · 2014: 87 · 2013: 56 · 2012: 78
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Keywords
- adenosine 5'-triphosphate, adenosine, purinergic signaling, purinergic receptors, endogenous signaling molecules, immunity, inflammation, immune regulation, immunostimulation, immune cell types, ectoenzymes, extracellular nucleotides
- MeSH terms
- Adenosine, Adenosine Triphosphate, Humans, Immune System, Immunity, Cellular, Macrophages, Neutrophils, Signal Transduction, Apoptosis
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