Rapid, noninflammatory and PS-dependent phagocytic clearance of necrotic cells.
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.
D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D018955:CD36 Antigens / Q000276:immunology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology; D005557:Formaldehyde / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D056484:Jumonji Domain-Containing Histone Demethylases; D019169:Jurkat Cells / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008081:Liposomes / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008563:Membrane Lipids / Q000032:analysis / Q000502:physiology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009336:Necrosis; D009840:Oligomycins / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010587:Phagocytosis / Q000276:immunology / Q000502:physiology*; D010718:Phosphatidylserines / Q000032:analysis / Q000502:physiology*; D011108:Polymers / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D019311:Staurosporine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D018950:Lipopolysaccharide Receptors; D008081:Liposomes; D008563:Membrane Lipids; D009840:Oligomycins; D009842:Oligopeptides; D010718:Phosphatidylserines; D011108:Polymers; C498708:Ptdsr protein, mouse; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C408123:phosphatidylserine receptor; D005557:Formaldehyde; D015759:Ionomycin; C059453:RGES peptide; C046617:arginyl-glycyl-aspartyl-serine; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; D019311:Staurosporine; D002118:Calcium; C003043:paraform