CoChat
Sign Up
Cited by 168Adenosine and Purinergic SignalingCalcium signaling and nucleotide metabolismIon Channels and Receptors

Extracellular ATP induces oscillations of intracellular Ca 2+ and membrane potential and promotes transcription of IL-6 in macrophages

Open access
Hanley, Peter J., Musset, Boris, Renigunta, Vijay, Limberg, Sven H., Dalpke, Alexander H., Sus, Rainer, Heeg, Klaus M., Preisig-Müller, Regina +1 more·2004·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0400733101PMC PMC439002
Open this paper in CoChat — free account

Abstract

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.

Integrity signals

Registry

Crossref · 10.1073/pnas.0400733101

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Uric acid can function as a DAMP by activating the inflammasome in APCs, stimulating production of IL-1β, IL-18 and IL-33 via caspase-1.

    “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]

  • Potential immunogenic signals from dying cells include surface-exposed proteins such as calreticulin and heat shock proteins, lipid moieties such as phosphatidylserine that flip to the outer leaflet, released proteins such as HMGB1, and extracellular nucleic acids and their degradation products (oligonucleotides, nucleotides, nucleosides, urate).

    “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]

  • Polynucleotides and oligonucleotides from degrading DNA or RNA can act on TLR3, TLR7, TLR8, or TLR9 and on intracellular receptors RIG1, MDA5, or LGP2, while ATP and its degradation products may activate or inhibit distinct classes of purinergic receptors.

    “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]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

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
ORCID
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
DOI
10.1073/pnas.0400733101
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review