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

doi:10.1084/jem.193.7.855

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 Oldenborg^a, Hattie D. Gresham^b^,c, and Frederik P. Lindberg^a

^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 bloodcells (RBCs) opsonized with autoantibody are recognized by macrophageFc ${gamma}$ and complement receptors. This triggers phagocytosis andelimination of RBCs from the circulation by splenic macrophages.We recently found that CD47 on unopsonized RBCs binds macrophagesignal regulatory protein ${alpha}$ (SIRP ${alpha}$ ), generating a negative signalthat prevents phagocytosis of the unopsonized RBCs. We showhere that clearance and phagocytosis of opsonized RBCs is alsoregulated by CD47-SIRP ${alpha}$ . The inhibition generated by CD47-SIRP ${alpha}$ interaction is strongly attenuated but not absent in mice withonly residual activity of the phosphatase Src homology 2 domain–containingprotein 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 integrationof the inhibitory SIRP ${alpha}$ signal with prophagocytic signals suchas from Fc ${gamma}$ and complement receptor activation. Thus, augmentationof inhibitory CD47-SIRP ${alpha}$ signaling may prevent or attenuate RBCclearance in AIHA.

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

Abbreviations used in this paper: AIHA, autoimmune hemolyticanemia; BMM, bone marrow–derived macrophage; HSA, humanserum albumin; IAP, integrin-associated protein; SHP, Src homology2 domain–containing protein tyrosine phosphatase; SIRP ${alpha}$ , signal regulatory protein ${alpha}$ .

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