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Cd47-Signal Regulatory Protein α (Sirpα) Regulates Fcγ and Complement Receptor–Mediated Phagocytosis
Open accessAbstract
In autoimmune hemolytic anemia (AIHA), circulating red blood cells (RBCs) opsonized with autoantibody are recognized by macrophage Fcγ 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 α (SIRPα), 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-SIRPα. The inhibition generated by CD47-SIRPα 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 SIRPα signaling in this system is mediated by SHP-1 phosphatase activity. The macrophage phagocytic response is controlled by an integration of the inhibitory SIRPα signal with prophagocytic signals such as from Fcγ and complement receptor activation. Thus, augmentation of inhibitory CD47-SIRPα signaling may prevent or attenuate RBC clearance in AIHA.
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Cited by
Majeti, R., Chao, M. P., Alizadeh, A. A., Pang, W. W., Jaiswal, S., Gibbs, K. D., van Rooijen, N., & Weissman, I. L. (2009) · Cell · doi:10.1016/j.cell.2009.05.045 · Cited by 1,752
Gardai, S. J., McPhillips, K. A., Frasch, S. C., Janssen, W. J., Starefeldt, A., Murphy-Ullrich, J. E., Bratton, D. L., Oldenborg, P.-A., Michalak, M., & Henson, P. M. (2005) · Cell · doi:10.1016/j.cell.2005.08.032 · Cited by 1,473
Self-citationThe ‘Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling
Neel, B. G., Gu, H., & Pao, L. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00091-4 · Cited by 1,249
Phagocytosis of Microbes: Complexity in Action
Underhill, D. M., & Ozinsky, A. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.103001.114744 · Cited by 1,124
Barclay, A. N., & van den Berg, T. K. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120142 · Cited by 841
Metadata
- Authors
- Oldenborg, P.-A., Gresham, H. D., & Lindberg, F. P.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2001-04-02
- Volume
- 193
- Issue
- 7
- Pages
- 855-862
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2117583909
- Cited by
- 452
- References
- 0
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Cd47-Signal Regulatory Protein α (Sirpα) Regulates Fcγ and Complement Receptor–Mediated Phagocytosis. https://app.cochat.ai/papers/10.1084/jem.193.7.855
- The paper
- Oldenborg, P.-A., Gresham, H. D., & Lindberg, F. P. (2001). Cd47-Signal Regulatory Protein α (Sirpα) Regulates Fcγ and Complement Receptor–Mediated Phagocytosis. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.193.7.855
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