Evidence map›Paper›PMID 26060214›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

Extracellular ATP protects against sepsis through macrophage P2X7 purinergic receptors by enhancing intracellular bacterial killing.

Balázs Csóka, Zoltán H Németh, Gábor Törő, Marco Idzko, Andreas Zech, Balázs Koscsó, Zoltán Spolarics, Luca Antonioli, Karolina Cseri, Katalin Erdélyi and 2 more

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Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
9.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 138 citations in OpenAlex.

  1. Review
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27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 2 countries.

Balázs Csóka*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Zoltán H Németh*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Gábor Törő*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Marco Idzko*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Andreas Zech*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Balázs Koscsó*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Zoltán Spolarics*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Luca Antonioli*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Karolina Cseri*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Katalin Erdélyi*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Pál Pacher*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
György Haskó*Department of Surgery and Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Surgery, Morristown Medical Center, Morristown, New Jersey, USA; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA haskoge@njms.rutgers.edu.
Rutgers New Jersey Medical SchoolNational Institute on Alcohol Abuse and Alcoholism · USRutgers, The State University of New Jersey · USUniversity Medical Center · USUniversity of Debrecen · HU

Funding

Mechanism of oxidative/nitrosative stress and inflammation-induced tissue injuryZIAAA000375 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI PACHER, PAL · 2009 to 2025
$27.8M
Purinergic signaling in trauma and sepsisR01GM066189 · NIGMS · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI HASKO, GEORGE · 2002 to 2020
$4.7M
Intramural NIH HHSNIGMS NIH HHS R01 GM066189NIGMS NIH HHS R01GM66189
6 · The paper itself

Abstract

Extracellular ATP binds to and signals through P2X7 receptors (P2X7Rs) to modulate immune function in both inflammasome-dependent and -independent manners. In this study, P2X7(-/-) mice, the pharmacological agonists ATP-magnesium salt (Mg-ATP; 100 mg/kg, EC50 ≈ 1.32 mM) and benzoylbenzoyl-ATP (Bz-ATP; 10 mg/kg, EC50 ≈ 285 μM), and antagonist oxidized ATP (oxi-ATP; 40 mg/kg, IC50 ≈ 100 μM) were used to show that P2X7R activation is crucial for the control of mortality, bacterial dissemination, and inflammation in cecal ligation and puncture-induced polymicrobial sepsis in mice. Our results with P2X7(-/-) bone marrow chimeric mice, adoptive transfer of peritoneal macrophages, and myeloid-specific P2X7(-/-) mice indicate that P2X7R signaling on macrophages is essential for the protective effect of P2X7Rs. P2X7R signaling protects through enhancing bacterial killing by macrophages, which is independent of the inflammasome. By using the connexin (Cx) channel inhibitor Gap27 (0.1 mg/kg, IC50 ≈ 0.25 μM) and pannexin channel inhibitor probenecid (10 mg/kg, IC50 ≈ 11.7 μM), we showed that ATP release through Cx is important for inhibiting inflammation and bacterial burden. In summary, targeting P2X7Rs provides a new opportunity for harnessing an endogenous protective immune mechanism in the treatment of sepsis.

Indexed as

Adenosine TriphosphateAdoptive TransferAnimalsBacteriaInflammasomesMacrophagesMiceMice, KnockoutReceptors, Purinergic P2X7SepsisSignal TransductionAdenosine TriphosphateInflammasomesReceptors, Purinergic P2X7connexininflammasomeinflammationpannexinphagocytosis

Identifiers

PMID26060214
PMCPMC4550379
OpenAlexW1793908464

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.