ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2016
Graft-Infiltrating Macrophages Adopt an M2 Phenotype and Are Inhibited by Purinergic Receptor P2X7 Antagonist in Chronic Rejection.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 76 citations in OpenAlex.
- Breaking the immune barrier: construction of cartilaginous organoids using alpha-1,3-galactosyltransferase-deficient pig cartilage-derived particles.Journal of translational medicine · 2026Article
- Molecular Imaging of Macrophages in Cardiovascular Diseases.Molecular imaging and biology · 2026Review
- Intracellular Calcium as a Regulator of Polarization and Target Reprogramming of Macrophages.International journal of molecular sciences · 2025Review
- Ultrasound molecular imaging of M2 macrophages for early detection of chronic rejection in heart transplantation.Journal of nanobiotechnology · 2025Article
- Unraveling the Roles of Macrophages in Vascularized Composite Allotransplantation.Biomedicines · 2025Review
- C-reactive protein orchestrates acute allograft rejection in vascularized composite allotransplantation via selective activation of monocyte subsets.Journal of advanced research · 2025Article
- P2X7 receptor in macrophage polarization and its implications in neuroblastoma tumor behavior.Purinergic signalling · 2025Article
- Macrophage Polarization in the Osteoarthritis Pathogenesis and Treatment.Orthopaedic surgery · 2025Review
- IL-6/IL-6R Signaling Blockade Alleviates Chronic Allograft Rejection by Modulating Germinal Center B Cells and Allograft Inflammation in Murine Cardiac Transplantation.Journal of inflammation research · 2025Article
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- Human leukocyte antigen class I antibody-activated endothelium promotes CD206+ M2 macrophage polarization and MMP9 secretion through TLR4 signaling and P-selectin in a model of antibody-mediated rejection and allograft vasculopathy.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024Article
- The Role of P2X7 Purinoceptors in the Pathogenesis and Treatment of Muscular Dystrophies.International journal of molecular sciences · 2023Review
- Adenovirus-IL-10 relieves chronic rejection after mouse heart transplantation by inhibiting miR-155 and activating SOCS5.International journal of medical sciences · 2023Article
- Neuropilin-1 is present on Foxp3+ T regulatory cell-derived small extracellular vesicles and mediates immunity against skin transplantation.Journal of extracellular vesicles · 2022Article
- Emerging Trends in Mesenchymal Stem Cells Applications for Cardiac Regenerative Therapy: Current Status and Advances.Stem cell reviews and reports · 2022Review
- Single-Cell RNA Sequencing Identifies Intra-Graft Population Heterogeneity in Acute Heart Allograft Rejection in Mouse.Frontiers in immunology · 2022Article
- The Role of Purinergic Signaling in Heart Transplantation.Frontiers in immunology · 2022Review
- P2X7 Receptor-Mediated Inflammation in Cardiovascular Disease.Frontiers in pharmacology · 2021Review
- M2 Macrophages Serve as Critical Executor of Innate Immunity in Chronic Allograft Rejection.Frontiers in immunology · 2021Review
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10 authors at 4 institutions in 2 countries.
Funding
Abstract
Macrophages exhibit diverse phenotypes and functions; they are also a major cell type infiltrating chronically rejected allografts. The exact phenotypes and roles of macrophages in chronic graft loss remain poorly defined. In the present study, we used a mouse heart transplant model to examine macrophages in chronic allograft rejection. We found that treatment of C57BL/6 mice with CTLA4 immunoglobulin fusion protein (CTLA4-Ig) prevented acute rejection of a Balb/c heart allograft but allowed chronic rejection to develop over time, characterized by prominent neointima formation in the graft. There was extensive macrophage infiltration in the chronically rejected allografts, and the graft-infiltrating macrophages expressed markers associated with M2 cells but not M1 cells. In an in vitro system in which macrophages were polarized into either M1 or M2 cells, we screened phenotypic differences between M1 and M2 cells and identified purinergic receptor P2X7 (P2x7r), an adenosine triphosphate (ATP)-gated ion channel protein that was preferentially expressed by M2 cells. We further showed that blocking the P2x7r using oxidized ATP (oATP) inhibited M2 induction in a dose-dependent fashion in vitro. Moreover, treatment of C57BL/6 recipients with the P2x7r antagonist oATP, in addition to CTLA4-Ig treatment, inhibited graft-infiltrating M2 cells, prevented transplant vasculopathy, and induced long-term heart allografts survival. These findings highlight the importance of the P2x7r-M2 axis in chronic rejection and establish P2x7r as a potential therapeutic target in suppression of chronic rejection.
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