Original Article

CD47-Signal Regulatory Protein (SIRP) Regulates Fc and Complement Receptor–mediated Phagocytosis

Correspondence to: Per-Arne Oldenborg, Dept. of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, SE-901 87 Umeå, Sweden. Tel:46-90-786-5974 Fax:46-90-786-6696 E-mail:per-arne.oldenborg{at}histocel.umu.se.

In autoimmune hemolytic anemia (AIHA), circulating red blood cells (RBCs) opsonized with autoantibody are recognized by macrophage Fc 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 (SIRP), 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. The inhibition generated by CD47-SIRP 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 signaling in this system is mediated by SHP-1 phosphatase activity. The macrophage phagocytic response is controlled by an integration of the inhibitory SIRP signal with prophagocytic signals such as from Fc and complement receptor activation. Thus, augmentation of inhibitory CD47-SIRP signaling may prevent or attenuate RBC clearance in AIHA.

Key Words: macrophages, autoimmunity, anemia, red blood cells, SHP-1

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