Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells.
Efficient phagocytosis of apoptotic cells is important for normal tissue development, homeostasis, and the resolution of inflammation. Although many receptors have been implicated in the clearance of apoptotic cells, the roles of these receptors in the engulfment process have not been well defined. We developed a novel system to distinguish between receptors involved in tethering of apoptotic cells versus those inducing their uptake. Our results suggest that regardless of the receptors engaged on the phagocyte, ingestion does not occur in the absence of phosphatidylserine (PS). Further, recognition of PS was found to be dependent on the presence of the PS receptor (PSR). Both PS and anti-PSR antibodies stimulated membrane ruffling, vesicle formation, and "bystander" uptake of cells bound to the surface of the phagocyte. We propose that the phagocytosis of apoptotic cells requires two events: tethering followed by PS-stimulated, PSR-mediated macropinocytosis.
Hoffmann
P R
PR
Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
deCathelineau
A M
AM
Ogden
C A
CA
Leverrier
Y
Y
Bratton
D L
DL
Daleke
D L
DL
Ridley
A J
AJ
Fadok
V A
VA
Henson
P M
PM
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D002462:Cell Membrane; D002478:Cells, Cultured; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010586:Phagocytes / Q000276:immunology; D010718:Phosphatidylserines / Q000276:immunology*; D010873:Pinocytosis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D020764:cdc42 GTP-Binding Protein / Q000276:immunology; D020830:rac1 GTP-Binding Protein / Q000276:immunology; D020742:rhoA GTP-Binding Protein / Q000276:immunology
D000911:Antibodies, Monoclonal; D010718:Phosphatidylserines; C498708:Ptdsr protein, mouse; D011956:Receptors, Cell Surface; C408123:phosphatidylserine receptor; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein