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First published online September 2, 2009
doi: 10.1242/10.1242/jcs.049569

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

¹ Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Korea
² Department of Biochemistry, School of Medicine, Dongguk University, Kyungju 780-714, Korea
³ Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany
⁴ Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia

^* Authors for correspondence (julia.kzhyshkowska{at}haut.ma.uni-heidelberg.de; iskim{at}knu.ac.kr)

Accepted 10 July 2009

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.

Key words: Stabilin-1, Phagocytosis, Aged RBC, Apoptotic cells, Macrophages

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