Recruitment of beta-2-glycoprotein 1 to cell surfaces in extrinsic and intrinsic apoptosis.
Apoptotic cells and phagocytes have developed a diverse array of distinct ligand-receptor systems that drive the recognition and uptake of dying cells. Phagocytes recognize apoptotic cells either directly, by binding to specific ligands at their cell surface, or indirectly, by binding to bridging proteins that bind these ligands. Previous observations showed that the plasma bridging protein beta2GP1, binds PS containing vesicles, and enhances their binding and engulfment by phagocytes in vitro. In this study we show that apoptotic cells injected intravenously and intraperitonealy into syngeneic mice recruited the PS binding protein, beta2GP1. Examination of peritoneal exudates and spleen thin sections showed that only the injected apoptotic cells picked up endogenous beta2GP1. Recovery of cells from the peritoneum showed that apoptotic cells bearing beta2GP1 were clustered around host peritoneal phagocytes. In addition, tissue sections from mice injected with Fas antibody showed colocalization of beta2GP1 with TUNEL-positive apoptotic cells. These results provide evidence that endogenous beta2GP1 binds apoptotic cells in vivo, suggesting that the protein plays an important physiologic role in the recognition of dying cells.
Balasubramanian
K
K
Department of Cancer Biology, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas, 77030, USA.
Maiti
S N
SN
Schroit
A J
AJ
D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D000925:Anticoagulants / Q000378:metabolism; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D008024:Ligands; D051379:Mice; D010586:Phagocytes; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism; D011485:Protein Binding; D013154:Spleen / Q000166:cytology; D053482:beta 2-Glycoprotein I
D017304:Annexin A5; D000925:Anticoagulants; D006023:Glycoproteins; D008024:Ligands; D010718:Phosphatidylserines; D053482:beta 2-Glycoprotein I