Target cell CD47 regulates macrophage activation and erythrophagocytosis

The ubiquitously expressed cell surface glycoprotein CD47 (integrin-associated protein, IAP) was originally identified as a regulator of integrin-dependent leukocyte responses to extracellular matrix proteins. However, it has been shown that CD47 has several important functions in addition to regulating integrin activation. Extensive studies in murine systems have shown that CD47 on erythrocytes and other cells can function as a regulator of target cell phagocytosis, by binding to the inhibitory receptor SIRPalpha on macrophages. In this way, macrophages 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 CD47-SIRPalpha interaction seems to be important in limiting destruction of host cells in experimental models of autoimmune diseases like autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia, where macrophages destroy antibody or complement opsonized cells.