The Journal of Experimental Medicine
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Published online 2 April 2001.
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© The Rockefeller University Press, 0022-1007/2001/4/855/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 7, April 2, 2001 855-862

Original Article

Cd47-Signal Regulatory Protein {alpha} (Sirp{alpha}) Regulates Fc{gamma} and Complement Receptor–Mediated Phagocytosis

Per-Arne Oldenborga, Hattie D. Greshamb,c, and Frederik P. Lindberga

a Division of Infectious Diseases, Department of Internal Medicine and Department of Molecular Microbiology and Pathogenesis, Washington University School of Medicine, St. Louis, Missouri 63110
b Research Service, Albuquerque Veterans Administration Medical Center, Albuquerque, New Mexico 87108
c Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, New Mexico 87131
Dept. of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, SE-901 87 Umeå, Sweden.46-90-786-669646-90-786-5974

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{gamma} 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 {alpha} (SIRP{alpha}), 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{alpha}. The inhibition generated by CD47-SIRP{alpha} 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{alpha} signaling in this system is mediated by SHP-1 phosphatase activity. The macrophage phagocytic response is controlled by an integration of the inhibitory SIRP{alpha} signal with prophagocytic signals such as from Fc{gamma} and complement receptor activation. Thus, augmentation of inhibitory CD47-SIRP{alpha} signaling may prevent or attenuate RBC clearance in AIHA.

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

Abbreviations used in this paper: AIHA, autoimmune hemolytic anemia; BMM, bone marrow–derived macrophage; HSA, human serum albumin; IAP, integrin-associated protein; SHP, Src homology 2 domain–containing protein tyrosine phosphatase; SIRP{alpha}, signal regulatory protein {alpha}.

© 2001 The Rockefeller University Press


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