The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Extracellular ATP induces oscillations of intracellular Ca 2+ and membrane potential and promotes transcription of IL-6 in macrophages
Open accessAbstract
The effects of low concentrations of extracellular ATP on cytosolic Ca 2+ , membrane potential, and transcription of IL-6 were studied in monocyte-derived human macrophages. During inflammation or infection many cells secrete ATP. We show here that application of 10 μM ATP or 10 μM UTP induces oscillations in cytosolic Ca 2+ with a frequency of ≈12 min -1 and oscillations in membrane potential. RT-PCR analysis showed expression of P2Y 1 , P2Y 2 , P2Y 11 , P2X 1 , P2X 4 , and P2X 7 receptors, large-conductance ( KCNMA1 and KCNMB1–4 ), and intermediate-conductance ( KCNN4 ) Ca 2+ -activated K + channels. The Ca 2+ oscillations were unchanged after removal of extracellular Ca 2+ , indicating that they were mainly due to movements of Ca 2+ between intracellular compartments. Comparison of the effects of different nucleotides suggests that the Ca 2+ oscillations were elicited by activation of P2Y 2 receptors coupled to phospholipase C. Patch–clamp experiments showed that ATP induced a transient depolarization, probably mediated by activation of P2X 4 receptors, followed by membrane potential oscillations due to opening of Ca 2+ -activated K + channels. We also found that 10 μM ATPγS increased transcription of IL-6 ≈40-fold within 2 h. This effect was abolished by blockade of P2Y receptors with 100 μM suramin. Our results suggest that ATP released from inflamed, damaged, or metabolically impaired cells represents a “danger signal” that plays a major role in activating the innate immune system.
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“Nucleotide products such as uric acid can also function as DAMPs, presumably by activating the inflammasome in APC, thereby stimulating the production of inflammatory cytokines such as interleukin-1β (IL-1β), IL-18 and IL-33, the secretion of which depends on the inflammasome-mediated activation of caspase-145,46.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [45]
In the citing paper
“Potential immunogenic signals emanating from dying cells include proteins that appear at the surface of stressed and dying cells (such as calreticulin and heat shock proteins, HSPs), lipid moieties that flip from the inner plasma membrane leaflet to the outer leaflet (such as phosphatidylserine) 38,60, proteins that are released into the supernatant of cells (such as HMGB1) 51, as well as nucleic”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [45]
In the citing paper
“Polynucleotides and oligonucleotides derived from degrading DNA or RNA can act on TLR3, TLR7, TLR8, or TLR9 as well as on intracellular receptors including RIG1, MDA5, or LGP2, while ATP and its degradation products may activate or inhibit distinct classes of purinergic receptors 45,108,109.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [45]
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Metadata
- Authors
- Hanley, P. J., Musset, B., Renigunta, V., Limberg, S. H., Dalpke, A. H., Sus, R., Heeg, K. M., Preisig-Müller, R., & Daut, J.
- Affiliations
- Philipps University of Marburg (DE)
- Institute of Physiology, Marburg University, Deutschhausstrasse 2, 35037 Marburg, Germany; and Institute of Microbiology, Marburg University, Pilgrimstein 2, 35037 Marburg, Germany
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-06-11
- Volume
- 101
- Issue
- 25
- Pages
- 9479-9484
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC439002
- OpenAlex
- W2000714729
- Cited by
- 168
- References
- 37
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 7 · 2016: 6 · 2015: 8 · 2014: 11 · 2013: 12 · 2012: 6
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- extracellular ATP, calcium oscillations, membrane potential oscillations, macrophages, P2Y receptors, P2X4 receptor, P2X7 receptor, P2Y2 receptor, purinergic signaling, ATP gamma S, suramin, phospholipase C, calcium-activated potassium channels, damage-associated molecular patterns, innate immunity
- MeSH terms
- Adenosine Triphosphate, Calcium, Cells, Cultured, Gene Expression Regulation, Humans, Macrophages, Membrane Potentials, Molecular Sequence Data, Oscillometry, Sodium, Transcription, Genetic, Interleukin-6, Receptors, Purinergic P2, Patch-Clamp Techniques, Calcium Signaling, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
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