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CD47 functions as a molecular switch for erythrocyte phagocytosis
Abstract
CD47 on erythrocytes inhibits phagocytosis through interaction with the inhibitory immunoreceptor SIRPα expressed by macrophages. Thus, the CD47-SIRPα interaction constitutes a negative signal for erythrocyte phagocytosis. However, we report here that CD47 does not only function as a "do not eat me" signal for uptake but can also act as an "eat me" signal. In particular, a subset of old erythrocytes present in whole blood was shown to bind and to be phagocytosed via CD47-SIRPα interactions. Furthermore, we provide evidence that experimental aging of erythrocytes induces a conformational change in CD47 that switches the molecule from an inhibitory signal into an activating one. Preincubation of experimentally aged erythrocytes with human serum before the binding assay was required for this activation. We also demonstrate that aged erythrocytes have the capacity to bind the CD47-binding partner thrombospondin-1 (TSP-1) and that treatment of aged erythrocytes with a TSP-1-derived peptide enabled their phagocytosis by human red pulp macrophages. Finally, CD47 on erythrocytes that had been stored for prolonged time was shown to undergo a conformational change and bind TSP-1. These findings reveal a more complex role for CD47-SIRPα interactions in erythrocyte phagocytosis, with CD47 acting as a molecular switch for controlling erythrocyte phagocytosis.
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“However, the major source of iron for systemic needs, such as red blood cell (RBC) maturation, are macrophages, which ingest senescent erythrocytes as well as haptoglobin-bound free hemoglobin and heme/Fe complexes released from lysed RBCs (Burger et al., 2012; Chow et al., 2013).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Burger et al., 2012
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Metadata
- Authors
- Burger, P., Hilarius-Stokman, P., de Korte, D., van den Berg, T. K., & van Bruggen, R.
- Affiliations
- Sanquin (NL)
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-06-07
- Volume
- 119
- Issue
- 23
- Pages
- 5512-5521
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1964791394
- Cited by
- 338
- References
- 46
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 31 · 2023: 34 · 2022: 28 · 2021: 27 · 2020: 27 · 2019: 27 · 2018: 9 · 2017: 28 · 2016: 19 · 2015: 17 · 2014: 22 · 2013: 14 · 2012: 9
- FWCI
- 8.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Physiology (medical) › Erythrocyte Function and Pathophysiology
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- CD47, erythrophagocytosis, SIRPα, thrombospondin-1, erythrocyte aging, macrophages, red pulp macrophages, red blood cell storage, erythrocyte clearance, molecular switches
- MeSH terms
- Animals, Antigens, Differentiation, Erythrocyte Aging, Erythrocytes, Cricetinae, Humans, Macrophages, Oligopeptides, Phagocytosis, Protein Conformation, Receptors, Immunologic, Transfection, CHO Cells, CD47 Antigen
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