The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment
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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“Examples of such signals are CD31 117 and CD47 118, although how these molecules are negated by cell death remains unexplored.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [118]
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Cites
Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics
Kerr, J. F. R., Wyllie, A. H., & Currie, A. R. (1972) · British Journal of Cancer · doi:10.1038/bjc.1972.33 · Cited by 15,673
Role of CD47 as a Marker of Self on Red Blood Cells
Oldenborg, P., Zheleznyak, A., Fang, Y., Lagenaur, C. F., Gresham, H. D., & Lindberg, F. P. (2000) · Science · doi:10.1126/science.288.5473.2051 · Cited by 1,975
Corpse clearance defines the meaning of cell death
Savill, J., & Fadok, V. A. (2000) · Nature · doi:10.1038/35037722 · Cited by 1,572
Self-citationSavill, J. S., Wyllie, A. H., Henson, J. E., Walport, M. J., Henson, P. M., & Haslett, C. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113970 · Cited by 1,536
Self-citationA receptor for phosphatidylserine-specific clearance of apoptotic cells
Fadok, V. A., Bratton, D. L., Rose, D. M., Pearson, A. M., Ezekowitz, R. A. B., & Henson, P. M. (2000) · Nature · doi:10.1038/35011084 · Cited by 1,491
PECAM-1 is required for transendothelial migration of leukocytes.
Müller, W. A., Weigl, S. A., Deng, X., & Phillips, D. M. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.2.449 · Cited by 1,151
Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis
Savill, J., Dransfield, I., Hogg, N., & Haslett, C. (1990) · Nature · doi:10.1038/343170a0 · Cited by 846
Self-citationSavill, J., Hogg, N., Ren, Y., & Haslett, C. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116019 · Cited by 818
Self-citationNewman, P. J. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119129 · Cited by 671
The Small Gtpase, Rap1, Mediates Cd31-Induced Integrin Adhesion
Reedquist, K. A., Ross, E. A., Koop, E. A., Wolthuis, R. M. F., Zwartkruis, F. J. T., van Kooyk, Y., Salmon, M., Buckley, C. D., & Bos, J. L. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.148.6.1151 · Cited by 415
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Regulation of cell death: the calcium–apoptosis link
Orrenius, S., Zhivotovsky, B., & Nicotera, P. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1150 · Cited by 3,060
A blast from the past: clearance of apoptotic cells regulates immune responses
Savill, J., Dransfield, I., Gregory, C. D., & Haslett, C. (2002) · Nature reviews. Immunology · doi:10.1038/nri957 · Cited by 1,574
Self-citationOverview of cell death signaling pathways
Jin, Z., & El‐Deiry, W. S. (2005) · Cancer Biology & Therapy · doi:10.4161/cbt.4.2.1508 · Cited by 1,345
Apoptotic cell clearance: basic biology and therapeutic potential
Poon, I. K. H., Lucas, C. D., Rossi, A. G., & Ravichandran, K. S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3607 · Cited by 1,223
Immunogenic and tolerogenic cell death
Green, D. R., Ferguson, T., Zitvogel, L., & Kroemer, G. (2009) · Nature Reviews Immunology · doi:10.1038/nri2545 · Cited by 1,176
Metadata
- 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
- Venue
- Nature
- Published
- 2002-07
- Volume
- 418
- Issue
- 6894
- Pages
- 200-203
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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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