The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Identification of a factor that links apoptotic cells to phagocytes
Abstract
Apoptotic cells are rapidly engulfed by phagocytes to prevent the release of potentially noxious or immunogenic intracellular materials from the dying cells, thereby preserving the integrity and function of the surrounding tissue. Phagocytes engulf apoptotic but not healthy cells, indicating that the apoptotic cells present a signal to the phagocytes, and the phagocytes recognize the signal using a specific receptor. Here, we report a factor that links apoptotic cells to phagocytes. We found that milk fat globule-EGF-factor 8 (MFG-E8), a secreted glycoprotein, was produced by thioglycollate-elicited macrophages. MFG-E8 specifically bound to apoptotic cells by recognizing aminophospholipids such as phosphatidylserine. MFG-E8, when engaged by phospholipids, bound to cells via its RGD (arginine-glycine-aspartate) motif--it bound particularly strongly to cells expressing alpha(v)beta(3) integrin. The NIH3T3 cell transformants that expressed a high level of alpha(v)beta(3) integrin were found to engulf apoptotic cells when MFG-E8 was added. MFG-E8 carrying a point mutation in the RGD motif behaved as a dominant-negative form, and inhibited the phagocytosis of apoptotic cells by peritoneal macrophages in vitro and in vivo. These results indicate that MFG-E8 secreted from activated macrophages binds to apoptotic cells, and brings them to phagocytes for engulfment.
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“Evidence also supports roles for Annexin I 122 and Gas-6 123 in recognizing PS on dying cells.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [122]
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Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles
Colombo, M., Raposo, G., & Théry, C. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101512-122326 · Cited by 6,186
Membrane vesicles as conveyors of immune responses
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Hoda, S. A., & Hoda, R. S. (2020) · American Journal of Clinical Pathology · doi:10.1093/ajcp/aqaa163 · Cited by 3,370
Apoptosis: controlled demolition at the cellular level
Taylor, R. C., Cullen, S. P., & Martin, S. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2312 · Cited by 2,708
Routes and mechanisms of extracellular vesicle uptake
Mulcahy, L. A., Pink, R. C., & Carter, D. R. F. (2014) · Journal of Extracellular Vesicles · doi:10.3402/jev.v3.24641 · Cited by 2,832
Metadata
- Authors
- Hanayama, R., Tanaka, M., Miwa, K., Shinohara, A., Iwamatsu, A., & Nagata, S.
- Affiliations
- The University of Osaka (JP)
- Japan Science and Technology Agency (JP)
- Kirin (Japan) (JP)
- Corresponding author
- Nagata, Shigekazu
- Venue
- Nature
- Published
- 2002-05
- Volume
- 417
- Issue
- 6885
- Pages
- 182-187
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2001567020
- Cited by
- 1,401
- References
- 31
- Citations by year
- 2026: 37 · 2025: 40 · 2024: 64 · 2023: 56 · 2022: 46 · 2021: 82 · 2020: 61 · 2019: 58 · 2018: 56 · 2017: 71 · 2016: 59 · 2015: 72 · 2014: 76 · 2013: 73 · 2012: 63
- FWCI
- 16.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Styrelsen för Internationellt Utvecklingssamarbete
- Sidaction
- Solar Energy Technologies Office
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- MFG-E8, efferocytosis, phagocytosis, phosphatidylserine, aminophospholipids, RGD motif, alpha v beta 3 integrin, macrophages, secreted glycoprotein, dominant-negative mutant, peritoneal macrophages
- MeSH terms
- Animals, Antibodies, Monoclonal, Antigens, Surface, Cell Adhesion, Cell Line, Cricetulus, Endocytosis, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Cricetinae, Membrane Glycoproteins, Milk Proteins, Oligopeptides, Phagocytes, Phosphatidylserines, Thioglycolates, Thymus Gland, 3T3 Cells, Apoptosis, Macrophages, Peritoneal, Receptors, Vitronectin, Mice
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