ArticleInflammation2013
The adenosine-dependent angiogenic switch of macrophages to an M2-like phenotype is independent of interleukin-4 receptor alpha (IL-4Rα) signaling.
Article in Inflammation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers.
What it found
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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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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.
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Who cites it
220 citing papers in PubMed, 356 citations in OpenAlex.
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- Targeted Photo-Induced Elimination of Tumor-Associated Macrophages Suppresses Cancer Progression in a Murine Model.Cancer science · 2026Article
- Microglia-Mediated Vascular Network Remodeling After Ischemic Stroke: An Immunovascular Repair Framework.Cells · 2026Review
- Macrophage 2 plays an important role in axonal lesions and vasculitis in Sjogren's syndrome complicated with peripheral neuropathy.Clinical rheumatology · 2026Article
- Review
- Navigating chemoresistance in triple-negative breast cancer: interplay between molecular signalling pathways and immune microenvironment.Molecular biology reports · 2026Review
- Recent progress in macrophage-mediated tendon injury and healing.Histology and histopathology · 2026Review
- Immunometabolic programming of macrophages and tumor-associated macrophages: metabolic pathways shaping polarization, immune regulation, and disease outcomes.Frontiers in immunology · 2026Review
- Inflammation at the maternal-fetal interface: a perspective on interacting risk factors for preterm birth in sub-Saharan African women living with HIV.Frontiers in immunology · 2026Review
- The Role and Mechanistic Effects of Methotrexate in the Treatment of Rheumatoid Arthritis.European journal of rheumatology · 2025Article
- Phase-Specific Evaluation of Sciatic Nerve Regeneration in Preclinical Studies: A Review of Functional Assessment, Emerging Therapies, and Translational Value.International journal of molecular sciences · 2025Review
- How do mechanical forces impact macrophages in the processes of mechanosensing and mechanotransduction?Journal of Zhejiang University. Science. B · 2025Review
- Immunomodulatory Biomaterials for Bone and Soft Tissue Chronic Inflammation Diseases.Small science · 2025Review
- Biomaterial-mediated macrophage polarization remodeling and sequential regulation: a potential strategy in bone infections treatment.Bone research · 2025Review
- NMRK2 leads to the depletion of CD8Oncogene · 2025Article
- Macrophages in endometriosis: key roles and emerging therapeutic opportunities-a narrative review.Reproductive biology and endocrinology : RB&E · 2025Review
- Role of Colony Stimulating Factor 1 (CSF-1) and Its Receptor CSF1R: Macrophage Repolarization for Glioblastoma Treatment.ACS pharmacology & translational science · 2025Review
- Cascade-Targeted Nanoparticles for Enhanced Gemcitabine Delivery and Adenosine Metabolism Modulation to Overcome Treatment Resistance in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dual roles and therapeutic targeting of tumor-associated macrophages in tumor microenvironments.Signal transduction and targeted therapy · 2025Review
160 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Murine macrophages are activated by interferon-γ (IFN-γ) and/or Toll-like receptor (TLR) agonists such as bacterial endotoxin (lipopolysaccharide [LPS]) to express an inflammatory (M1) phenotype characterized by the expression of nitric oxide synthase-2 (iNOS) and inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-12. In contrast, Th2 cytokines IL-4 and IL-13 activate macrophages by inducing the expression of arginase-1 and the anti-inflammatory cytokine IL-10 in an IL-4 receptor-α (IL-4Rα)-dependent manner. Macrophages activated in this way are designated as "alternatively activated" (M2a) macrophages. We have shown previously that adenosine A2A receptor (A(2A)R) agonists act synergistically with TLR2, TLR4, TLR7, and TLR9 agonists to switch macrophages into an "M2-like" phenotype that we have termed "M2d." Adenosine signaling suppresses the TLR-dependent expression of TNF-α, IL-12, IFN-γ, and several other inflammatory cytokines by macrophages and induces the expression of vascular endothelial growth factor (VEGF) and IL-10. We show here using mice lacking a functional IL-4Rα gene (IL-4Rα(-/-) mice) that this adenosine-mediated switch does not require IL-4Rα-dependent signaling. M2d macrophages express high levels of VEGF, IL-10, and iNOS, low levels of TNF-α and IL-12, and mildly elevated levels of arginase-1. In contrast, M2d macrophages do not express Ym1, Fizz1 (RELM-α), or CD206 at levels greater than those induced by LPS, and dectin-1 expression is suppressed. The use of these markers in vivo to identify "M2" macrophages thus provides an incomplete picture of macrophage functional status and should be viewed with caution.
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What OpenQuestion holds
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.