ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Loss of Cell Surface CD47 Clustering Formation and Binding Avidity to SIRPα Facilitate Apoptotic Cell Clearance by Macrophages.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 110 citations in OpenAlex.
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- SIRPα extracellular domain shed from neutrophils by ADAM10 aggravates sepsis via initiating nitric oxide release from erythrocyte.Journal of advanced research · 2026Article
- Bon appétit, your phagocyte.Cell death discovery · 2026Review
- MERTK coordinates efferocytosis by regulating integrin localization and activation.Journal of cell science · 2026Article
- Targeting phagocytosis checkpoints for cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Membrane-derived biomimetic nanovesicles in anti-tumor immunotherapy: Advances and outlook.Acta pharmaceutica Sinica. B · 2026Review
- CD47 Promotes, While Exposure to Apoptotic Cells Destroys the Fusion Program of Differentiating Myoblasts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Cannabidiol Regulates CD47 Expression and Apoptosis in Jurkat Leukemic Cells Dependent upon VDAC-1 Oligomerization.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The CD47 signaling axis regulates the formation and vulnerability of atherosclerotic plaques: mechanism analysis and targeting strategies.Frontiers in immunology · 2026Review
- Pathological Interplay of ROS With Myofibroblasts: An Impediment to Corneal Restitution.Oxidative medicine and cellular longevity · 2026Review
- Review
- CD47 signaling in aging and age-related diseases: mechanisms, challenges, and therapeutic opportunities.Biogerontology · 2025Review
- Acquired Hypolipoproteinemia and Hemophagocytic Lymphohistiocytosis: A Case Series and Review.Hematology reports · 2025Review
- Clearing the Path: Exploring Apoptotic Cell Clearance in Inflammatory and Autoimmune Disorders for Therapeutic Advancements.Molecular biotechnology · 2025Review
- Brain endothelial cells as phagocytes: mechanisms and implications.Fluids and barriers of the CNS · 2025Review
- Super-resolution microscopy unveils the nanoscale organization and self-limiting clustering of CD47 in human erythrocytes.Journal of molecular cell biology · 2025Article
- Targeting the NLRP3 in macrophages contributes to senescence cell clearance in radiation-induced skin injury.Journal of translational medicine · 2025Article
- Biochemical and biophysical mechanisms macrophages use to tune phagocytic appetite.Journal of cell science · 2025Review
- Cancer stem cells: advances in the glucose, lipid and amino acid metabolism.Molecular and cellular biochemistry · 2024Review
- Resolvin E1 improves efferocytosis and rescues severe aplastic anemia in mice.Cell death & disease · 2024Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
CD47, a self recognition marker expressed on tissue cells, interacts with immunoreceptor SIRPα expressed on the surface of macrophages to initiate inhibitory signaling that prevents macrophage phagocytosis of healthy host cells. Previous studies suggested that cells may lose surface CD47 during aging or apoptosis to enable phagocytic clearance. In the current study, we demonstrate that the level of cell surface CD47 is not decreased, but the distribution pattern of CD47 is altered, during apoptosis. On nonapoptotic cells, CD47 molecules are clustered in lipid rafts forming punctates on the surface, whereas on apoptotic cells, CD47 molecules are diffused on the cell surface following the disassembly of lipid rafts. We show that clustering of CD47 in lipid rafts provides a high binding avidity for cell surface CD47 to ligate macrophage SIRPα, which also presents as clusters, and elicits SIRPα-mediated inhibitory signaling that prevents phagocytosis. In contrast, dispersed CD47 on the apoptotic cell surface is associated with a significant reduction in the binding avidity to SIRPα and a failure to trigger SIRPα signal transduction. Disruption of plasma membrane lipid rafts with methyl-β-cyclodextrin diffuses CD47 clusters, leading to a decrease in the cell binding avidity to SIRPα and a concomitant increase in cells being engulfed by macrophages. Taken together, our study reveals that CD47 normally is clustered in lipid rafts on nonapoptotic cells but is diffused in the plasma membrane when apoptosis occurs; this transformation of CD47 greatly reduces the strength of CD47-SIRPα engagement, resulting in the phagocytosis of apoptotic cells.
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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.