ArticleJCI insight2018
Macrophage P2X4 receptors augment bacterial killing and protect against sepsis.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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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.
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Who cites it
63 citing papers in PubMed, 111 citations in OpenAlex.
- Neuroglial P2YJournal of neuroinflammation · 2026Article
- BRD4 modulates antimicrobial defense via non-canonical NRF2 activation in macrophages to confer protection against sepsis.PLoS pathogens · 2026Article
- Article
- P2X4 receptors on myeloid cells mediate tissue injury in a model of trauma and hemorrhagic shock in male mice.Purinergic signalling · 2026Article
- Purinergic signaling in the gut neuro-glial-immune axis: mechanisms of homeostasis, inflammation, and gastrointestinal dysfunction.Frontiers in gastroenterology (Lausanne, Switzerland) · 2026Review
- Nucleotide Metabolic Reprogramming in Sepsis: From Immune-Cell Fate to Organ Injury and Precision Therapeutics.Journal of inflammation research · 2026Review
- Macrophage TMEM175-Mediated Transcriptional Regulation of Cathepsins Drives Bacterial Killing in Sepsis.Journal of immunology research · 2026Article
- Ivermectin modulates macrophage activity and enhances bacterial clearance in Pseudomonas aeruginosa acute pneumonia.Molecular and cellular biochemistry · 2026Article
- P2X4 receptors on myeloid cells mediate tissue injury in a murine model of trauma and hemorrhagic shock.Research square · 2025Article
- M1-like macrophages regulate T cell infiltration in colorectal cancer through P2X4 receptor.iScience · 2025Article
- P2RX4 promotes hepatocellular carcinoma progression via calcium-mediated PI3K/AKT activation and immune remodeling.World journal of surgical oncology · 2025Article
- Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics.Journal of advanced research · 2025Review
- Purinergic signaling in the battlefield of viral infections.Purinergic signalling · 2025Review
- Finely ordered intracellular domain harbors an allosteric site to modulate physiopathological function of P2X3 receptors.Nature communications · 2024Article
- Impaired ATP hydrolysis in blood plasma contributes to age-related neutrophil dysfunction.Immunity & ageing : I & A · 2024Article
- Effect of ethanol exposure on innate immune response in sepsis.Journal of leukocyte biology · 2024Review
- CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice.JCI insight · 2024Article
- ATP breakdown in plasma of children limits the antimicrobial effectiveness of their neutrophils.Purinergic signalling · 2023Article
- ATPergic signaling disruption in human sepsis as a potential source of biomarkers for clinical use.Clinical and experimental medicine · 2023Article
- Targeting of phagolysosomes containing conidia of the fungus Aspergillus fumigatus with polymeric particles.Applied microbiology and biotechnology · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 4 countries.
Funding
Abstract
The macrophage is a major phagocytic cell type, and its impaired function is a primary cause of immune paralysis, organ injury, and death in sepsis. An incomplete understanding of the endogenous molecules that regulate macrophage bactericidal activity is a major barrier for developing effective therapies for sepsis. Using an in vitro killing assay, we report here that the endogenous purine ATP augments the killing of sepsis-causing bacteria by macrophages through P2X4 receptors (P2X4Rs). Using newly developed transgenic mice expressing a bioluminescent ATP probe on the cell surface, we found that extracellular ATP levels increase during sepsis, indicating that ATP may contribute to bacterial killing in vivo. Studies with P2X4R-deficient mice subjected to sepsis confirm the role of extracellular ATP acting on P2X4Rs in killing bacteria and protecting against organ injury and death. Results with adoptive transfer of macrophages, myeloid-specific P2X4R-deficient mice, and P2rx4 tdTomato reporter mice indicate that macrophages are essential for the antibacterial, antiinflammatory, and organ protective effects of P2X4Rs in sepsis. Pharmacological targeting of P2X4Rs with the allosteric activator ivermectin protects against bacterial dissemination and mortality in sepsis. We propose that P2X4Rs represent a promising target for drug development to control bacterial growth in sepsis and other infections.
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Registered trials
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.