Cited by 338Phagocytosis and Immune RegulationErythrocyte Function and PathophysiologyBlood groups and transfusion

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CD47 functions as a molecular switch for erythrocyte phagocytosis

Burger, Patrick, Hilarius-Stokman, Petra, de Korte, Dirk, van den Berg, Timo K., van Bruggen, Robin·2012·Blood

DOI 10.1182/blood-2011-10-386805

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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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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
DOI: 10.1182/blood-2011-10-386805
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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CD47 functions as a molecular switch for erythrocyte phagocytosis

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