title: Macrophage-mediated clearance of cells undergoing caspase-3-independent death.
abstract: Little is known of the functions of caspases in mediating the surface changes required for phagocytosis of dying cells. Here we investigate the role played by the effector caspase, caspase-3 in this process using the caspase-3-defective MCF-7 breast carcinoma line and derived caspase-3-expressing transfectants. Our results indicate that, while certain typical features of apoptosis induced by etoposide--namely classical morphological changes and the ability to degrade DNA into oligonucleosomal fragments - are caspase-3-dependent, loss of cell adhesion to plastic and the capacity to interact with, and to be phagocytosed by, human monocyte-derived macrophages - both by CD14-dependent and CD14-independent mechanisms--do not require caspase-3. Furthermore, both etoposide-induced caspase-3-positive and -negative MCF-7 cells suppressed proinflammatory cytokine release by macrophages. These results demonstrate directly that cell surface changes that are sufficient for anti-inflammatory clearance by human macrophages can be regulated independently of stereotypical features of the apoptosis programme that require caspase-3.
authors.affiliation: MRC Center for Inflammation Research, University of Edinburgh, UK.
authors.forename: C
authors.initials: C
authors.lastname: Turner
authors.forename: A
authors.initials: A
authors.lastname: Devitt
authors.forename: K
authors.initials: K
authors.lastname: Parker
authors.forename: M
authors.initials: M
authors.lastname: MacFarlane
authors.forename: M
authors.initials: M
authors.lastname: Giuliano
authors.forename: G M
authors.initials: GM
authors.lastname: Cohen
authors.forename: C D
authors.initials: CD
authors.lastname: Gregory
mesh_terms: D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005047:Etoposide / Q000494:pharmacology*; D049452:Green Fluorescent Proteins; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008164:Luminescent Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D017304:Annexin A5; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008164:Luminescent Proteins; D010718:Phosphatidylserines; D049452:Green Fluorescent Proteins; D005047:Etoposide; D004247:DNA; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases