ArticlePloS one2013
Autocrine regulation of macrophage activation via exocytosis of ATP and activation of P2Y11 receptor.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 118 citations in OpenAlex.
- Follistatin-like protein 1 enhances NLRP3 inflammasome-mediated IL-1β secretion from monocytes and macrophages.European journal of immunology · 2014Trial
- Article
- Exocytosed ATP as a therapeutic target for inflammatory and metabolic diseases.Frontiers in pharmacology · 2026Review
- VNUT-mediated ATP release suppresses T helper 1 (TScience advances · 2025Article
- Intracellular Calcium as a Regulator of Polarization and Target Reprogramming of Macrophages.International journal of molecular sciences · 2025Review
- M1-like macrophages regulate T cell infiltration in colorectal cancer through P2X4 receptor.iScience · 2025Article
- Role of shear stress-induced red blood cell released ATP in atherosclerosis.American journal of physiology. Heart and circulatory physiology · 2025Article
- Deficiency of P2RY11 causes narcolepsy and attenuates the recruitment of neutrophils and macrophages in the inflammatory response in zebrafish.Cell biology and toxicology · 2024Article
- DAMPs and radiation injury.Frontiers in immunology · 2024Review
- An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential.Cancer cell international · 2023Review
- SLC17A9-PTHLH-EMT axis promotes proliferation and invasion of clear renal cell carcinoma.iScience · 2023Article
- A liquid chromatography-tandem mass spectrometry based method for the quantification of adenosine nucleotides and NAD precursors and products in various biological samples.Frontiers in immunology · 2023Article
- Purinergic signaling via P2X receptors and mechanisms of unregulated ATP release in the outer retina and age-related macular degeneration.Frontiers in neuroscience · 2023Review
- Effects of Stromal Cell Conditioned Medium and Antipurinergic Treatment on Macrophage Phenotype.Tissue engineering. Part C, Methods · 2022Article
- Article
- A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling.Purinergic signalling · 2022Review
- Galectin-9 deficiency exacerbates lipopolysaccharide-induced hypothermia and kidney injury.Clinical and experimental nephrology · 2022Article
- Extracellular vesicles participate in the pathogenesis of sepsis.Frontiers in cellular and infection microbiology · 2022Review
- Extracellular ATP and Macropinocytosis: Their Interactive and Mutually Supportive Roles in Cell Growth, Drug Resistance, and EMT in Cancer.Sub-cellular biochemistry · 2022Review
- Quinacrine is not a vital fluorescent probe for vesicular ATP storage.Purinergic signalling · 2021Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is important to understand the mechanisms that regulate macrophage activation to establish novel therapies for inflammatory diseases, such as sepsis; a systemic inflammatory response syndrome generally caused by bacterial lipopolysaccharide (LPS). In this study, we investigated the involvement of extracellular ATP-mediated autocrine signaling in LPS-induced macrophage activation. We show here that ATP release via exocytosis, followed by activation of P2Y11 receptor, is a major pathway of the macrophage activation, leading to release of cytokines. Treatment of human monocyte THP-1 cells with LPS induced rapid ATP release from cells, and this release was blocked by knockdown of SLC17A9 (vesicular nucleotide transporter, VNUT), which is responsible for exocytosis of ATP. ATP-enriched vesicles were found in cytosol of THP-1 cells. These data suggest the involvement of vesicular exocytosis in the release of ATP. Knockdown of SLC17A9, the P2Y11 antagonist NF157 or knockdown of P2Y11 receptor significantly suppressed both M1-type polarization and IL-6 production in THP-1 cells, indicating an important role of activation of P2Y11 receptor by released ATP in macrophage activation. Next, the effect of NF157 on LPS-induced immune activation was examined in vivo. Administration of LPS to mice caused increase of serum IL-1ß, IL-6, IL-12 and TNF-alpha levels at 3-24 h after the administration. Pre-treatment of LPS-treated mice with NF157 suppressed both elevation of proinflammatory cytokines in serum and M1 polarization of peritoneal/spleen macrophages. Moreover, post-treatment with NF157 at 30 min after administration of LPS also suppressed the elevation of serum cytokines levels. We conclude that vesicular exocytosis of ATP and autocrine, positive feedback through P2Y11 receptors is required for the effective activation of macrophages. Consequently, P2Y11 receptor antagonists may be drug candidates for treatment of inflammatory diseases such as sepsis.
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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.