CD47: A Cell Surface Glycoprotein Which Regulates Multiple Functions of Hematopoietic Cells in Health and Disease
Figure 4
CD47 regulates phagocytosis of host cells by interacting with SIRPα. (a) CD47 on viable normal host cells can bind to SIRPα on a phagocytic cell (e.g., a macrophage (M)), which induces tyrosine phosphorylation of SIRPα ITIMS and recruitment of SHP-1. This can inhibit prophagocytic signaling through Fcγ receptors, complement receptors (CR), or LRP-1. Phagocytosis inhibition may involve signaling through Syk and PI3 kinase and inhibition of nonmuscle myosin type IIA (NMMIIA). (b) On apoptotic cells, CD47 becomes clustered in the plasma membrane and may be segregated away from domains containing ligands for prophagocytic receptors, here exemplified by calreticulin (crt) binding to LRP-1. However, most likely this principle involves also other prophagocytic receptors (receptor x). Clustered CD47 may also bind to SIRPα without inducing inhibition of phagocytosis, but may rather promote tethering of the apoptotic cell to the phagocyte. This function may also involve TSP-1 and so far uncharacterized mechanisms that can also promote phagocytosis. (c) Cancer cells may increase their expression of CD47 to strengthen the inhibitory signals through SIRPα and to more potently inhibit phagocytosis mediated by Fcγ receptors and other prophagocytic receptors (receptor x).
