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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“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]
Citations
Cites
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394
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
Decoding the Patterns of Self and Nonself by the Innate Immune System
Medzhitov, R., & Janeway, C. A. (2002) · Science · doi:10.1126/science.1068883 · Cited by 2,154
Calcium oscillations increase the efficiency and specificity of gene expression
Dolmetsch, R. E., Xu, K., & Lewis, R. S. (1998) · Nature · doi:10.1038/31960 · Cited by 1,896
Impaired immune and acute-phase responses in interleukin-6-deficient mice
Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., & Köhler, G. (1994) · Nature · doi:10.1038/368339a0 · Cited by 1,768
Danger signals: SOS to the immune system
Gallucci, S., & Matzinger, P. (2001) · Current Opinion in Immunology · doi:10.1016/s0952-7915(00)00191-6 · Cited by 1,204
Dai, X.-M., Ryan, G. R., Hapel, A. J., Dominguez, M. G., Russell, R. G., Kapp, S., Sylvestre, V., & Stanley, E. R. (2002) · Blood · doi:10.1182/blood.v99.1.111 · Cited by 1,184
IL-6 switches the differentiation of monocytes from dendritic cells to macrophages
Chomarat, P., Banchereau, J., Davoust, J. M., & Palucka, K. (2000) · Nature Immunology · doi:10.1038/82763 · Cited by 906
The two faces of IL-6 on Th1/Th2 differentiation
Diehl, S. A., & Rincón, M. (2002) · Molecular Immunology · doi:10.1016/s0161-5890(02)00210-9 · Cited by 873
Calcium signaling mechanisms in T lymphocytes.
Lewis, R. S. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.497 · Cited by 860
Nucleotide receptors: an emerging family of regulatory molecules in blood cells
Virgilio, F. D., Chiozzi, P., Ferrari, D., Falzoni, S., Sanz, J. M., Morelli, A., Torboli, M., Bolognesi, G., & Baricordi, O. R. (2001) · Blood · doi:10.1182/blood.v97.3.587 · Cited by 702
Ferrari, D., Chiozzi, P., Falzoni, S., Susino, M. D., Melchiorri, L., Baricordi, O. R., & Virgilio, F. D. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.3.1451 · Cited by 616
A human intermediate conductance calcium-activated potassium channel
Ishii, T. M., Silvia, C. P., Hirschberg, B., Bond, C. T., Adelman, J. P., & Maylie, J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.21.11651 · Cited by 612
Extracellular ATP or ADP Induce Chemotaxis of Cultured Microglia through Gi/o-Coupled P2Y Receptors
Honda, S., Sasaki, Y., Ohsawa, K., Imai, Y., Nakamura, Y., Inoue, K., & Kohsaka, S. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-06-01975.2001 · Cited by 561
Lazarowski, E. R., Boucher, R. C., & Harden, T. K. (2003) · Molecular Pharmacology · doi:10.1124/mol.64.4.785 · Cited by 550
Molecular pharmacology of P2Y-receptors
von Kügelgen, I., & Wetter, A. (2000) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s002100000310 · Cited by 483
A two-step, two-signal model for the primary activation of precursor helper T cells
Bretscher, P. A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.1.185 · Cited by 386
Molecular Properties and Physiological Roles of Ion Channels in the Immune System
Cahalan, M. D., Wulff, H., & Chandy, K. G. (2001) · Journal of Clinical Immunology · doi:10.1023/a:1010958907271 · Cited by 238
Fairbairn, I. P., Stober, C. B., Kumararatne, D. S., & Lammas, D. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.6.3300 · Cited by 237
Ion channels in microglia (brain macrophages)
Eder, C. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.275.2.c327 · Cited by 196
Advances in signalling by extracellular nucleotides
Communi, D., Janssens, R., Suarez-Huerta, N., Robaye, B., & Boeynaems, J. (2000) · Cellular Signalling · doi:10.1016/s0898-6568(00)00083-8 · Cited by 187
K+ channels and the microglial respiratory burst
Khanna, R., Roy, L., Zhu, X., & Schlichter, L. C. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.280.4.c796 · Cited by 182
Shigemoto‐Mogami, Y., Koizumi, S., Tsuda, M., Ohsawa, K., Kohsaka, S., & Inoue, K. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00514.x · Cited by 173
Tuyt, L., Dokter, W. H. A., Birkenkamp, K. U., Koopmans, S., Lummen, C., Kruijer, W., & Vellenga, E. (1999) · PubMed · Cited by 139
Regulation of a TRPM7-like Current in Rat Brain Microglia
Jiang, X., Newell, E. W., & Schlichter, L. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304487200 · Cited by 135
Disordered Cellular Migration and Angiogenesis in cd39- Null Mice
Goepfert, C., Sundberg, C., Sévigny, J., Enjyoji, K., Hoshi, T., Csizmadia, E., & Robson, S. C. (2001) · Circulation · doi:10.1161/hc5001.100663 · Cited by 132
Tuyt, L., Dokter, W. H. A., Birkenkamp, K. U., Koopmans, S., Lummen, C., Kruijer, W., & Vellenga, E. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.8.4893 · Cited by 123
Spontaneous and induced membrane hyperpolarizations in macrophages
Gallin, E. K., Wiederhold, M. L., Lipsky, P. E., & Rosenthal, A. S. (1975) · Journal of Cellular Physiology · doi:10.1002/jcp.1040860510 · Cited by 117
Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells
Mitani, H., Katayama, N., Araki, H., Ohishi, K., Kobayashi, K., Suzuki, H., Nishii, K., Masuya, M., Yasukawa, K., Minami, N., et al. (2000) · British Journal of Haematology · doi:10.1046/j.1365-2141.2000.02020.x · Cited by 99
P2X4, P2Y1 and P2Y2 receptors on rat alveolar macrophages
Bowler, J. W., Bailey, R. J., North, R. A., & Surprenant, A. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705459 · Cited by 95
Bost, K. L., & Mason, M. J. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.1.285 · Cited by 60
Schilling, T., Repp, H., Richter, H., Koschinski, A., Heinemann, U., Dreyer, F., & Eder, C. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00534-6 · Cited by 58
Schmid‐Antomarchi, H., Schmid‐Alliana, A., Romey, G., Ventura, M. A., Breittmayer, V. A., Millet, M.-A., Husson, H., Moghrabi, B., Lazdunski, M., & Rossi, B. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.12.6209 · Cited by 55
Calcium responses elicited by nucleotides in macrophages. Interaction between two receptor subtypes.
Alonso-Torre, S. R., & Trautmann, A. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)46678-6 · Cited by 49
ATP- and UTP-induced currents in macrophages and macrophage polykaryons
de Albuquerque, C. R., Oliveira, S.-N. M. C. G., Coutinho‐Silva, R., Oliveira-Castro, G. M., & Persechini, P. M. (1993) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1993.265.6.c1663 · Cited by 28
Flagged first, then by citations
Research works printed but not linked: 1
- Ralevic, V. & Burnstock, G. (1998) Pharmacol. Rev. 50, 413-492.9755289
Cited by
Sorted by citations
Borsellino, G., Kleinewietfeld, M., Mitri, D. D., Sternjak, A., Diamantini, A., Giometto, R., Höpner, S., Centonze, D., Bernardi, G., Dell’Acqua, M. L., et al. (2007) · Blood · doi:10.1182/blood-2006-12-064527 · Cited by 1,287
Immunogenic and tolerogenic cell death
Green, D. R., Ferguson, T., Zitvogel, L., & Kroemer, G. (2009) · Nature Reviews Immunology · doi:10.1038/nri2545 · Cited by 1,176
Bours, M. J. L., Swennen, E. L. R., Di Virgilio, F., Cronstein, B. N., & Dagnelie, P. C. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.04.013 · Cited by 1,030
The P2X7 Receptor: A Key Player in IL-1 Processing and Release
Ferrari, D., Pizzirani, C., Adinolfi, E., Lemoli, R. M., Curti, A., Idzko, M., Panther, E., & Di Virgilio, F. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.7.3877 · Cited by 1,025
Ion Channels in Innate and Adaptive Immunity
Feske, S., Wulff, H., & Skolnik, E. Y. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112212 · Cited by 787
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
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