Stabilin-1 mediates phosphatidylserine-dependent clearance of cell corpses in alternatively activated macrophages.
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.
Park
Seung-Yoon
SY
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Korea.
Jung
Mi-Yeon
MY
Lee
Sung-Jin
SJ
Kang
Kae-Bok
KB
Gratchev
Alexei
A
Riabov
Vladimir
V
Kzhyshkowska
Julia
J
Kim
In-San
IS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000737:chemistry; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D016201:Receptors, Lymphocyte Homing / Q000737:chemistry / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; D010718:Phosphatidylserines; D016201:Receptors, Lymphocyte Homing; C449926:STAB1 protein, human; C449927:STAB2 protein, human; D015847:Interleukin-4; D004815:Epidermal Growth Factor; D003907:Dexamethasone