Abstract
MCF-7 cells undergo autophagic death upon tamoxifen treatment. Plated on non-adhesive substratum these cells died by anoikis while inducing autophagy as revealed by monodansylcadaverine staining, elevated light-chain-3 expression and electron microscopy. Both de novo and anoikis-derived autophagic dying cells were engulfed by human macrophages and MCF-7 cells. Inhibition of autophagy by 3-methyladenine abolished engulfment of cells dying through de novo autophagy, but not those dying through anoikis. Blocking exposure of phosphatidylserine (PS) on both dying cell types inhibited phagocytosis by MCF-7 but not by macrophages. Gene expression profiling showed that though both types of phagocytes expressed full repertoire of the PS recognition and signaling pathway, macrophages could evolve during engulfment of de novo autophagic cells the potential of calreticulin-mediated processes as well. Our data suggest that cells dying through autophagy and those committing anoikis with autophagy may engage in overlapping but distinct sets of clearance mechanisms in professional and non-professional phagocytes.
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Abbreviations
- AV:
-
autophagic vacuoles
- CFDA-SE:
-
carboxyfluoresceindiacetatesuccinimidyl ester
- CMTMR:
-
5-(and-6)-(((4-chloromethyl)benzoyl)amino)tetramethylrhodamine
- DAPK:
-
death-associated protein kinase
- DRP-1:
-
death-related protein kinase-1
- FITC:
-
fluorescein isothiocyanate
- LC3:
-
light-chain-3
- MCSF:
-
macrophage colony stimulating factor
- MDC:
-
monodansylcadaverin
- PCD:
-
programmed cell death
- PI3K:
-
phosphatidyl-inositol 3-kinase
- poly-HEMA:
-
poly(2-hydroxyethylmethacrylate)
- PS:
-
phosphatidylserine
- PI:
-
propidium iodide
- TAM:
-
tamoxifen ([α-(4-β-N-dimethylaminoethoxy)-phenyl-α′-ethyl-trans-stilbene])
- TEM:
-
transmission electron microscopy
- TLDA:
-
TaqMan low-density array
- TNF:
-
tumor necrosis factor
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Acknowledgements
This study was supported by grants from the Hungarian National Research Fund (OTKA TO43083, TS44798), National Research and Development Office (NKFP 1A/008/04) and from EU (QLK3-CT-2002 02017). Special thanks to Dr Zsuzsa Szondy for helpful discussions.
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Petrovski, G., Zahuczky, G., Katona, K. et al. Clearance of dying autophagic cells of different origin by professional and non-professional phagocytes. Cell Death Differ 14, 1117–1128 (2007). https://doi.org/10.1038/sj.cdd.4402112
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DOI: https://doi.org/10.1038/sj.cdd.4402112
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