Document Detail


Rapid, noninflammatory and PS-dependent phagocytic clearance of necrotic cells.
MedLine Citation:
PMID:  14502239     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In pathological situations, different modes of cell death are observed, and information on the role and uptake of nonapoptotic corpses is scarce. Here, we modeled two distinct forms of death in human Jurkat T cells treated with staurosporine: classical apoptosis under normal culture conditions and programmed death with necrotic morphology under ATP-depleting conditions (necPCD). When offered to phagocytes, both types of cell corpses (but not heat-killed unscheduled necrotic cells) reduced the release of the proinflammatory cytokine TNF from the macrophages. The necPCD cells were efficiently engulfed by macrophages and microglia, and from mixtures of necPCD and apoptotic cells macrophages preferentially engulfed the necrotic cells. Using a newly developed assay, we demonstrated that phosphatidylserine is translocated to the surface of such necrotic cells. We demonstrate that this can occur independently of calcium signals, and that surface phosphatidylserine is essential for the uptake of necrotic cells by both human macrophages and murine microglia.
Authors:
U A Hirt; M Leist
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell death and differentiation     Volume:  10     ISSN:  1350-9047     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-09-22     Completed Date:  2004-06-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  1156-64     Citation Subset:  IM    
Affiliation:
Faculty of Biology, University of Konstanz, X911, D-78457 Konstanz, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Annexin A5 / pharmacology
Antibodies, Monoclonal / immunology,  pharmacology
Antigens, CD14 / immunology
Antigens, CD36 / immunology
Apoptosis / physiology
Calcium / pharmacology,  physiology
Cell Line
Cell Membrane / chemistry
Cells, Cultured
Escherichia coli / immunology
Formaldehyde / pharmacology
Humans
Inflammation / immunology,  metabolism*
Ionomycin / pharmacology
Jumonji Domain-Containing Histone Demethylases
Jurkat Cells / pathology
Liposomes / pharmacology
Macrophages / cytology,  drug effects,  metabolism
Membrane Lipids / analysis,  physiology
Mice
Microglia / cytology,  drug effects,  metabolism
Microscopy, Confocal
Microscopy, Fluorescence
Necrosis
Oligomycins / pharmacology
Oligopeptides / pharmacology
Phagocytosis / immunology,  physiology*
Phosphatidylserines / analysis,  physiology*
Polymers / pharmacology
Receptors, Cell Surface / antagonists & inhibitors
Staurosporine / pharmacology
Tumor Necrosis Factor-alpha / metabolism,  secretion
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Antibodies, Monoclonal; 0/Antigens, CD14; 0/Antigens, CD36; 0/Liposomes; 0/Membrane Lipids; 0/Oligomycins; 0/Oligopeptides; 0/Phosphatidylserines; 0/Polymers; 0/Ptdsr protein, mouse; 0/Receptors, Cell Surface; 0/Tumor Necrosis Factor-alpha; 0/phosphatidylserine receptor; 30525-89-4/paraform; 50-00-0/Formaldehyde; 56092-81-0/Ionomycin; 62996-74-1/Staurosporine; 7440-70-2/Calcium; 91037-65-9/arginyl-glycyl-aspartyl-serine; 93674-97-6/RGES peptide; EC 1.14.11.-/JMJD6 protein, human; EC 1.14.11.-/Jumonji Domain-Containing Histone Demethylases

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