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Apoptotic Cells Induce Migration of Phagocytes via Caspase-3-Mediated Release of a Lipid Attraction Signal
Open accessAbstract
Efficient engulfment of the intact cell corpse is a critical end point of apoptosis, required to prevent secondary necrosis and inflammation. The presentation of "eat-me" signals on the dying cell is an important part of this process of recognition and engulfment by professional phagocytes. Here, we present evidence that apoptotic cells secrete chemotactic factor(s) that stimulate the attraction of monocytic cells and primary macrophages. The activation of caspase-3 in the apoptotic cell was found to be required for the release of this chemotactic factor(s). The putative chemoattractant was identified as the phospholipid, lysophosphatidylcholine. Further analysis showed that lysophosphatidylcholine was released from apoptotic cells due to the caspase-3 mediated activation of the calcium-independent phospholipase A(2). These data suggest that in addition to eat-me signals, apoptotic cells display attraction signals to ensure the efficient removal of apoptotic cells and prevent postapoptotic necrosis.
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“However, autoimmunity has been observed in mice in which phagocytes lack the G-protein coupled receptor G2A41, which is required for the response to lysophosphatidylcholine 42”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [41]
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“Conversely, by the expression of anti-inflammatory cytokines such caspases might directly cleave the putative inhibitor and as transforming growth factor- (Fadok et al., 1998). thereby release iPLA2.”
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Metadata
- Authors
- Lauber, K., Bohn, E., Kröber, S. M., Xiao, Y.-J., Blumenthal, S. G., Lindemann, R. K., Marini, P., Wiedig, C., Zobywalski, A., Baksh, S., Xu, Y., Autenrieth, I. B., Schulze-Osthoff, K., Belka, C., Stuhler, G., & Wesselborg, S.
- Affiliations
- University of Tübingen (DE)
- Cleveland Clinic (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Wesselborg, Sebastian
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2003-06
- Volume
- 113
- Issue
- 6
- Pages
- 717-730
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2159330173
- Cited by
- 967
- References
- 35
- Citations by year
- 2026: 31 · 2025: 31 · 2024: 42 · 2023: 41 · 2022: 50 · 2021: 40 · 2020: 32 · 2019: 31 · 2018: 43 · 2017: 33 · 2016: 37 · 2015: 39 · 2014: 44 · 2013: 43 · 2012: 36
- FWCI
- 15.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3699 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- 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 › Autophagy in Disease and Therapy
- Keywords
- efferocytosis, caspase-3, lysophosphatidylcholine, phagocyte migration, macrophages, monocytic cells, calcium-independent phospholipase A2, eat-me signals, secondary necrosis, inflammation
- MeSH terms
- Animals, Chemotaxis, Enzyme Inhibitors, Eukaryotic Cells, Humans, Inflammation, Lysophosphatidylcholines, Phagocytes, Phagocytosis, Phospholipases A, Protein Synthesis Inhibitors, Signal Transduction, Ankyrin Repeat, Apoptosis, HT29 Cells, COS Cells, Caspases, Cell Surface Extensions, Lipid Metabolism, Mice, Caspase 3
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