Role of CD47 in erythroid cells and in autoimmunity.
The cell surface glycoprotein CD47 (Integrin-associated protein/IAP) was originally identified as a regulator of integrin-dependent responses to extracellular matrix proteins. However, CD47 is ubiquitously expressed, also by cells that do not express integrins. Thus, during the last few years, it has been shown that CD47 has several important functions besides assisting integrin activation. This review will focus on the role of CD47 in erythrocytes. In these cells, CD47 was found to be an important link in the interaction between the band 3 complex and the Rh complex in the maintenance of erythrocyte membrane integrity. CD47 can also function as a marker of self on erythrocytes, and likely also on other cells, by binding to the inhibitory receptor SIRPalpha. In this way, SIRPalpha-expressing cells, like macrophages and dendritic cells, are less likely to phagocytose an autoimmune sensitized cell with CD47 on its surface than a CD47-deficient cell where this inhibitory mechanism will not be engaged. The interaction between CD47 and SIRPalpha seems to be important to limit destruction of host cells in autoimmune diseases like autoimmune hemolytic anemia (AIHA), where macrophages destroy antibody or complement opsonized cells.
Oldenborg
Per-Arne
PA
Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, SE-901 87 Umeå, Sweden. per-arne.oldenborg@histocel.umu.se
D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000502:physiology*; D051928:CD47 Antigen; D003713:Dendritic Cells / Q000378:metabolism; D004905:Erythrocyte Aging / Q000502:physiology; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008958:Models, Molecular; D039842:Neural Cell Adhesion Molecule L1 / Q000502:physiology; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000502:physiology; D012204:Rh-Hr Blood-Group System / Q000378:metabolism; D017634:Self Tolerance / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D001457:Anion Exchange Protein 1, Erythrocyte; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001324:Autoantigens; D051928:CD47 Antigen; C497894:CD47 protein, human; C497895:Cd47 protein, mouse; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D011971:Receptors, Immunologic; D012204:Rh-Hr Blood-Group System