Macrophage-mediated clearance of cells undergoing caspase-3-independent death.
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.
Turner
C
C
MRC Center for Inflammation Research, University of Edinburgh, UK.
Devitt
A
A
Parker
K
K
MacFarlane
M
M
Giuliano
M
M
Cohen
G M
GM
Gregory
C D
CD
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
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