ArticleBMC immunology2023
Prevention of M2 polarization and temporal limitation of differentiation in monocytes by extracellular ATP.
Article in BMC immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- P2X7 receptor: An emerging therapeutic target in acute myeloid leukemia (Review).International journal of oncology · 2026Review
- CD39 mRNA therapy attenuates localized acute inflammation: A novel anti-inflammatory strategy using cationic nanoliposomes.Molecular therapy. Nucleic acids · 2026Article
- Intracellular Calcium as a Regulator of Polarization and Target Reprogramming of Macrophages.International journal of molecular sciences · 2025Review
- Intrinsic immunosuppressive features of monocytes suppress CAR-T19 through IL-1 pathway modulation in mantle cell lymphoma.Molecular therapy. Oncology · 2025Article
- P2X7 Receptor in Dendritic Cells and Macrophages: Implications in Antigen Presentation and T Lymphocyte Activation.International journal of molecular sciences · 2024Review
- Functional interleukin-4 releasing microparticles impact THP-1 differentiated macrophage phenotype.Frontiers in bioengineering and biotechnology · 2024Article
- Blocking P2Y2 purinergic receptor prevents the development of lipopolysaccharide-induced acute respiratory distress syndrome.Frontiers in immunology · 2023Article
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundElevated levels of extracellular adenosine triphosphate (ATP) modulate immunologic pathways and are considered to be a danger signal in inflammation, lung fibrosis and cancer. Macrophages can be classified into two main types: M1 macrophages are classically activated, pro-inflammatory macrophages, whereas M2 macrophages are alternatively activated, pro-fibrotic macrophages. In this study, we examined the effect of ATP on differentiation of native human monocytes into these macrophage subtypes. We characterized M1 and M2 like macrophages by their release of Interleukin-1beta (IL-1β) and Chemokine (C-C motif) ligand 18 (CCL18), respectively.
resultsMonocytes were stimulated with ATP or the P2X7 receptor agonist Benzoylbenzoyl-ATP (Bz-ATP), and the production of various cytokines was analyzed, with a particular focus on CCL18 and IL-1β, along with the expression of different purinergic receptors. Over a 72 h period of cell culture, monocytes spontaneously differentiated to M2 like macrophages, as indicated by an increased release of CCL18. Immediate stimulation of monocytes with ATP resulted in a dose-dependent reduction in CCL18 release, but had no effect on the concentration of IL-1β. In contrast, delayed stimulation with ATP had no effect on either CCL18 or IL-1β release. Similar results were observed in a model of inflammation using lipopolysaccharide-stimulated human monocytes. Stimulation with the P2X7 receptor agonist Bz-ATP mimicked the effect of ATP on M2-macrophage differentiation, indicating that P2X7 is involved in ATP-induced inhibition of CCL18 release. Indeed, P2X7 was downregulated during spontaneous M2 differentiation, which may partially explain the ineffectiveness of late ATP stimulation of monocytes. However, pre-incubation of monocytes with PPADS, Suramin (unselective P2X- and P2Y-receptor blockers) and KN62 (P2X7-antagonist) failed to reverse the reduction of CCL18 by ATP.
conclusionsATP prevents spontaneous differentiation of monocytes into M2-like macrophages in a dose- and time-dependent manner. These effects were not mediated by P2X and P2Y receptors.
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