Role of CD47 as a marker of self on red blood cells.
The immune system recognizes invaders as foreign because they express determinants that are absent on host cells or because they lack "markers of self" that are normally present. Here we show that CD47 (integrin-associated protein) functions as a marker of self on murine red blood cells. Red blood cells that lacked CD47 were rapidly cleared from the bloodstream by splenic red pulp macrophages. CD47 on normal red blood cells prevented this elimination by binding to the inhibitory receptor signal regulatory protein alpha (SIRPalpha). Thus, macrophages may use a number of nonspecific activating receptors and rely on the presence or absence of CD47 to distinguish self from foreign. CD47-SIRPalpha may represent a potential pathway for the control of hemolytic anemia.
Oldenborg
P A
PA
Division of Infectious Diseases, Department of Internal Medicine, Campus Box 8051, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Zheleznyak
A
A
Fang
Y F
YF
Lagenaur
C F
CF
Gresham
H D
HD
Lindberg
F P
FP
D000743:Anemia, Hemolytic / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000943:Antigens, Differentiation; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004002:Clodronic Acid / Q000494:pharmacology; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D008081:Liposomes; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis; D010766:Phosphorylation; D011971:Receptors, Immunologic; D017634:Self Tolerance; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; C497895:Cd47 protein, mouse; D008081:Liposomes; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D011971:Receptors, Immunologic; D004002:Clodronic Acid