CD 47 - Signal Regulatory Protein a ( SIRP a ) Regulates Fc g and Complement Receptor – mediated Phagocytosis

In autoimmune hemolytic anemia (AIHA), circulating red blood cells (RBCs) opsonized with autoantibody are recognized by macrophage Fc g and complement receptors. This triggers phagocytosis and elimination of RBCs from the circulation by splenic macrophages. We recently found that CD47 on unopsonized RBCs binds macrophage signal regulatory protein a (SIRP a ), generating a negative signal that prevents phagocytosis of the unopsonized RBCs. We show here that clearance and phagocytosis of opsonized RBCs is also regulated by CD47-SIRP a . The inhibition generated by CD47-SIRP a interaction is strongly attenuated but not absent in mice with only residual activity of the phosphatase Src homology 2 domain–containing protein tyrosine phosphatase (SHP)-1, suggesting that most SIRP a signaling in this system is mediated by SHP-1 phosphatase activity. The macrophage phagocytic response is controlled by an integration of the inhibitory SIRP a signal with prophagocytic signals such as from Fc g and complement receptor activation. Thus, augmentation of inhibitory CD47-SIRP a signaling may prevent or attenuate RBC clearance in AIHA.