Cited by 390Phagocytosis and Immune RegulationCell death mechanisms and regulationCell Adhesion Molecules Research

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Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment

Brown, Simon, Heinisch, Isabelle, Ross, Ewan, Shaw, Kate, Buckley, Chris D., Savill, John·2002·Nature

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Abstract

Macrophage recognition and ingestion of 'self' cells undergoing apoptosis in vivo protects tissues from the toxic contents of dying cells and modulates macrophage regulation of inflammatory and immune responses. However, the complex molecular mechanisms mediating macrophage discrimination between viable and apoptotic cells are poorly understood. In particular, little is known of why viable nucleated cells are not engulfed by macrophages. To reveal active repulsion of viable cells and to seek specific capture or 'tethering' of apoptotic cells, we studied macrophage binding of viable and apoptotic leukocytes under conditions of flow. We found that homophilic ligation of CD31 (ref. 4) on viable leukocytes promoted their active, temperature-dependent detachment under low shear, whereas such CD31-mediated detachment was disabled in apoptotic leukocytes, promoting tight binding and macrophage ingestion of dying cells. Here we propose that CD31 (also known as platelet-endothelial cell adhesion molecule-1, PECAM-1) is an example of a cell-surface molecule that prevents phagocyte ingestion of closely apposed viable cells by transmitting 'detachment' signals, and which changes function on apoptosis, promoting tethering of dying cells to phagocytes.

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Authors: Brown, S., Heinisch, I., Ross, E., Shaw, K., Buckley, C. D., & Savill, J.
Affiliations: Centre for Inflammation Research (GB)
University of Birmingham (GB)
Corresponding author: Brown, Simon
ORCID: Brown, Simon
Ross, Ewan
Savill, John
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2002-07
Volume: 418
Issue: 6894
Pages: 200-203
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature00811
OpenAlex: W1968736434
Cited by: 390
References: 21
Citations by year: 2026: 4 · 2025: 9 · 2024: 11 · 2023: 10 · 2022: 10 · 2021: 17 · 2020: 17 · 2019: 18 · 2018: 6 · 2017: 16 · 2016: 12 · 2015: 8 · 2014: 17 · 2013: 16 · 2012: 15
FWCI: 7.89
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
University of Birmingham Research Portal (University of Birmingham) (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Wellcome Trust
Topics: Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords: apoptosis, CD31, macrophage phagocytosis, cell detachment, leukocyte tethering, homophilic adhesion, shear flow, cell surface signaling
MeSH terms: Cell Adhesion, Cell Survival, Cells, Cultured, Endocytosis, Humans, Leukocytes, Macrophages, Proteolipids, Signal Transduction, Apoptosis, Platelet Endothelial Cell Adhesion Molecule-1

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Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment

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