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Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.
- V. Fadok, D. Bratton, A. Konowal, P. W. Freed, J. Westcott, P. Henson
- Biology, MedicineJournal of Clinical Investigation
- 15 February 1998
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.
C1q and Mannose Binding Lectin Engagement of Cell Surface Calreticulin and Cd91 Initiates Macropinocytosis and Uptake of Apoptotic Cells
Evidence is provided that C1q and mannose binding lectin (MBL), a member of the collectin family of proteins, bind to apoptotic cells and stimulate ingestion of these by ligation on the phagocyte surface of the multifunctional protein, calreticulin.
A receptor for phosphatidylserine-specific clearance of apoptotic cells
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.
Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages.
- V. Fadok, D. Voelker, P. Campbell, J. Cohen, D. Bratton, P. Henson
- BiologyJournal of Immunology
- 1 April 1992
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.
Corpse clearance defines the meaning of cell death
Appoptosis marks unwanted cells with 'eat me' signals that direct recognition, engulfment and degradation by phagocytes allow scavenger cells to confer meaning upon cell death.
Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation.
In vivo that direct instillation of apoptotic cells enhanced the resolution of acute inflammation, and apoptotic cell recognition and clearance, via exposure of PS and ligation of its receptor, induce TGF-beta1 secretion, resulting in accelerated resolution of inflammation.
A Hierarchical Role for Classical Pathway Complement Proteins in the Clearance of Apoptotic Cells in Vivo
Differential Effects of Apoptotic Versus Lysed Cells on Macrophage Production of Cytokines: Role of Proteases1
It is suggested that anti-inflammatory signals can be given by PtdSer-containing cell membranes, whether from early apoptotic, late apoptotic or lysed cells, but can be overcome by proteases liberated during lysis.
Phosphatidylserine (PS) induces PS receptor–mediated macropinocytosis and promotes clearance of apoptotic cells
The results suggest that regardless of the receptors engaged on the phagocyte, ingestion does not occur in the absence of phosphatidylserine (PS), and recognition of PS was found to be dependent on the presence of the PS receptor (PSR).
Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells.
The results suggest that the mechanism by which apoptotic cells are recognized and phagocytosed by macrophages is determined by the subpopulation of macrophage studied.