Abstract
Rapid phagocytic clearance of apoptotic cells is crucial for the prevention of both inflammation and autoimmune responses. Phosphatidylserine (PS) at the external surface of the plasma membrane has been proposed to function as a general ‘eat me’ signal for apoptotic cells. Although several soluble bridging molecules have been suggested for the recognition of PS, the PS-specific membrane receptor that binds directly to the exposed PS and provides a tickling signal has yet to be definitively identified. In this study, we provide evidence that stabilin-2 is a novel PS receptor, which performs a key function in the rapid clearance of cell corpses. It recognizes PS on aged red blood cells and apoptotic cells, and mediates their engulfment. The downregulation of stabilin-2 expression in macrophages significantly inhibits phagocytosis, and anti-stabilin-2 monoclonal antibody provokes the release of the anti-inflammatory cytokine, transforming growth factor-β. Furthermore, the results of time-lapse video analyses indicate that stabilin-2 performs a crucial function in the rapid clearance of aged and apoptotic cells. These data indicate that stabilin-2 is the first of the membrane PS receptors to provide tethering and tickling signals, and may also be involved in the resolution of inflammation and the prevention of autoimmunity.
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Accession codes
Abbreviations
- PS:
-
phosphatidylserine
- RBCs:
-
red blood cells
- TGF-β:
-
transforming growth factor-β
- PSR:
-
phosphatidylserine receptor
- LDL:
-
low-density lipoprotein
- PC:
-
phosphatidylcholine
- NBD:
-
7-nitrobenz-2-oxa-1,3-diazole
- HMDMs:
-
human monocyte-derived macrophages
- mAb:
-
monoclonal antibody
- shRNA:
-
short hairpin RNA
- PMA:
-
phorbol myristate acetate
- FITC:
-
fluorecein-5-isothiocyanate.
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Acknowledgements
This work was supported by a National Research Laboratory Program (M10104000036-01J0000-01610); by the Grant No. RTI04-01-01 from the Regional Technology Innovation Program of the MOCIE, Advanced Medical Technology Cluster for Diagnosis and Prediction at Kyungpook National University from MOCIE; and by the Brain Korea 21 Project, in 2007.
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Supplementary Information accompanies the paper on Cell Death and Differentiation website (http://www.nature.com/cdd)
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Park, SY., Jung, MY., Kim, HJ. et al. Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ 15, 192–201 (2008). https://doi.org/10.1038/sj.cdd.4402242
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DOI: https://doi.org/10.1038/sj.cdd.4402242
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