Article

Stabilin-1 mediates phosphatidylserine-dependent clearance of cell corpses in alternatively activated macrophages.

Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Korea.
Journal of Cell Science (impact factor: 6.11). 10/2009; 122(Pt 18):3365-73. DOI:10.1242/jcs.049569 pp.3365-73
Source: PubMed

ABSTRACT Stabilin-1 is specifically expressed in alternatively activated macrophages. These macrophages participate in anti-inflammatory and healing processes, and display a high phagocytic capacity. In this study, we provide evidence that stabilin-1 is a membrane receptor that performs a crucial function in the clearance of cell corpses. Stabilin-1 is expressed on the cell surface of alternatively activated macrophages and is recruited to the sites of recognition and engulfment of apoptotic bodies, as well as to early phagosomes. Blocking stabilin-1 in macrophages results in defective engulfment of aged red blood cells. Ectopic expression of stabilin-1 induces the binding and engulfment of aged cells in mouse fibroblast L cells. The binding and phagocytosis are dependent on phosphatidylserine (PS), which is well known as an engulfing ligand. Furthermore, using PS-coated beads, we demonstrate that PS directly interacts with stabilin-1 and is sufficient for stabilin-1-mediated phagocytosis. EGF-like domain repeat in stabilin-1 is responsible for PS recognition and binding. Thus, our results demonstrate that stabilin-1, found on alternatively activated macrophages, is a phagocytic receptor mediating the clearance of apoptotic cells in a PS-dependent manner. Therefore, this protein might play an important role in the maintenance of tissue homeostasis and prevention of autoimmunity.

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Keywords

activated macrophages
 
apoptotic cells
 
Blocking stabilin-1
 
cell corpses
 
cell surface
 
crucial function
 
defective engulfment
 
EGF-like domain repeat
 
engulfing ligand
 
healing processes
 
macrophages results
 
membrane receptor
 
mouse fibroblast L cells
 
phagocytic capacity
 
phagocytic receptor mediating
 
PS-coated beads
 
red blood cells
 
stabilin-1
 
stabilin-1 induces
 
stabilin-1-mediated phagocytosis