Cited by 967Phagocytosis and Immune RegulationCell death mechanisms and regulationAutophagy in Disease and Therapy

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Apoptotic Cells Induce Migration of Phagocytes via Caspase-3-Mediated Release of a Lipid Attraction Signal

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Lauber, Kirsten, Bohn, Erwin, Kröber, Stefan Martin, Xiao, Yi-jin, Blumenthal, Sibylle G., Lindemann, Ralph K., Marini, Patrizia, Wiedig, Carolin, Zobywalski, Anke, Baksh, Shairaz, Xu, Yan, Autenrieth, Ingo B., Schulze-Osthoff, Klaus, Belka, Claus, Stuhler, Gernot, Wesselborg, Sebastian·2003·Cell

DOI 10.1016/s0092-8674(03)00422-7

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Abstract

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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Self-citation
Retracted
Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1
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Self-citation
Retracted
Sphingosylphosphorylcholine and Lysophosphatidylcholine Are Ligands for the G Protein-coupled Receptor GPR4
Zhu, K., Baudhuin, L. M., Hong, G., Williams, F. S., Cristina, K. L., Kabarowski, J. H. S., Witte, O. N., & Xu, Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008057200 · Cited by 242
Self-citation
Retracted
Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.
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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.”
Background
Caspase-3 Is Required for DNA Fragmentation and Morphological Changes Associated with Apoptosis
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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: Lauber, Kirsten
Bohn, Erwin
Lindemann, Ralph K.
Baksh, Shairaz
Xu, Yan
Autenrieth, Ingo B.
Belka, Claus
Wesselborg, Sebastian
Venue: Cell
Publisher: Elsevier BV
Published: 2003-06
Volume: 113
Issue: 6
Pages: 717-730
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(03)00422-7
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
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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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Apoptotic Cells Induce Migration of Phagocytes via Caspase-3-Mediated Release of a Lipid Attraction Signal

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