Journal ArticleDOI
A receptor for phosphatidylserine-specific clearance of apoptotic cells
Valerie A. Fadok,Donna L. Bratton,David M. Rose,Alan Pearson,R. Alan B. Ezekewitz,Peter M. Henson +5 more
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TLDR
Using phage display, a gene that appears to recognize phosphatidylserine on apoptotic cells is cloned and shown to be highly homologous to genes of unknown function in Caenorhabditis elegans and Drosophila melanogaster, suggesting that phosphatido-serine recognition on apoptosis cells during their removal by phagocytes is highly conserved throughout phylogeny.Abstract:
The culmination of apoptosis in vivo is phagocytosis of cellular corpses. During apoptosis, the asymmetry of plasma membrane phospholipids is lost, which exposes phosphatidylserine externally1,2,3,4. The phagocytosis of apoptotic cells can be inhibited stereospecifically by phosphatidylserine and its structural analogues, but not by other anionic phospholipids, suggesting that phosphatidylserine is specifically recognized1,5,6,7,8,9,10. Using phage display, we have cloned a gene that appears to recognize phosphatidylserine on apoptotic cells. Here we show that this gene, when transfected into B and T lymphocytes, enables them to recognize and engulf apoptotic cells in a phosphatidylserine-specific manner. Flow cytometric analysis using a monoclonal antibody suggested that the protein is expressed on the surface of macrophages, fibroblasts and epithelial cells; this antibody, like phosphatidylserine liposomes, inhibited the phagocytosis of apoptotic cells and, in macrophages, induced an anti-inflammatory state. This candidate phosphatidylserine receptor is highly homologous to genes of unknown function in Caenorhabditis elegans and Drosophila melanogaster, suggesting that phosphatidylserine recognition on apoptotic cells during their removal by phagocytes is highly conserved throughout phylogeny.read more
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Cell Death: Critical Control Points
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Regulation of cell death: the calcium-apoptosis link.
TL;DR: The dual role of Ca2+ in living organisms is discussed in this paper, where it has been shown that cellular Ca 2+ overload, or perturbation of intracellular Ca2 + compartmentalization, can cause cytotoxicity and trigger either apoptotic or necrotic cell death.
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NF-κB at the crossroads of life and death
Michael Karin,Anning Lin +1 more
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Apoptosis: controlled demolition at the cellular level
TL;DR: This work has shown that during the demolition phase of apoptosis, members of the caspase family of cysteine proteases target several hundred proteins for restricted proteolysis in a controlled manner that minimizes damage and disruption to neighbouring cells and avoids the release of immunostimulatory molecules.
References
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Journal Article
Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages.
Valerie A. Fadok,Dennis R. Voelker,Priscilla A. Campbell,J. John Cohen,D L Bratton,Peter M. Henson +5 more
TL;DR: The data suggest that macrophages specifically recognize phosphatidylserine that is exposed on the surface of lymphocytes during the development of apoptosis, and suggest that apoptotic lymphocytes lose membrane phospholipid asymmetry and expose phosphorus on the outer leaflet of the plasma membrane.
Journal ArticleDOI
Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.
TL;DR: The results suggest that binding and/or phagocytosis of apoptotic cells induces active antiinflammatory or suppressive properties in human macrophages, likely that resolution of inflammation depends not only on the removal of apoptosis but on active suppression of inflammatory mediator production.
Journal ArticleDOI
Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl.
Seamus J. Martin,Chris P. M. Reutelingsperger,A J McGahon,J. A. Rader,R. C. A. A. Van Schie,Drake LaFace,Douglas R. Green +6 more
TL;DR: It is shown that PS externalization is an early and widespread event during apoptosis of a variety of murine and human cell types, regardless of the initiating stimulus, and precedes several other events normally associated with this mode of cell death.
Journal ArticleDOI
Wnt signaling: a common theme in animal development
Ken M. Cadigan,Roel Nusse +1 more
TL;DR: Current understanding of Wnt function and signaling mechanisms is reviewed in a comparative approach, highlighting novelty and underscoring questions that remain, and putting emphasis on the latest findings.
Journal ArticleDOI
Membrane protein structure prediction: Hydrophobicity analysis and the positive-inside rule
TL;DR: In this paper, a new strategy for predicting the topology of bacterial inner membrane proteins is proposed on the basis of hydrophobicity analysis, automatic generation of a set of possible topologies and ranking of these according to the positive inside rule.