Cd47-Signal Regulatory Protein α (Sirpα) Regulates Fcγ and Complement Receptor–Mediated Phagocytosis
| Autor: | Frederik P. Lindberg, Per-Arne Oldenborg, Hattie D. Gresham |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Erythrocytes Protein tyrosine phosphatase Complement receptor Mice 0302 clinical medicine Immunology and Allergy Receptors Immunologic Neural Cell Adhesion Molecules 0303 health sciences Membrane Glycoproteins Protein Tyrosine Phosphatase Non-Receptor Type 6 autoimmunity Intracellular Signaling Peptides and Proteins hemic and immune systems Opsonin Proteins anemia Receptors Complement 3. Good health Cell biology 030220 oncology & carcinogenesis SHP-1 Original Article Female Signal transduction Autoimmune hemolytic anemia Signal Transduction Cell Survival Phagocytosis Immunology Bone Marrow Cells CD47 Antigen Neural Cell Adhesion Molecule L1 Biology 03 medical and health sciences Antigens CD medicine Signal-regulatory protein alpha Animals Opsonin Crosses Genetic 030304 developmental biology Macrophages CD47 Receptors IgG medicine.disease Antigens Differentiation Molecular biology Mice Mutant Strains Mice Inbred C57BL Protein Tyrosine Phosphatases Carrier Proteins red blood cells |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.193.7.855 |
| Popis: | In autoimmune hemolytic anemia (AIHA), circulating red blood cells (RBCs) opsonized with autoantibody are recognized by macrophage Fcgamma 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 (SIRPalpha), 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-SIRPalpha. The inhibition generated by CD47-SIRPalpha 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 SIRPalpha signaling in this system is mediated by SHP-1 phosphatase activity. The macrophage phagocytic response is controlled by an integration of the inhibitory SIRPalpha signal with prophagocytic signals such as from Fcgamma and complement receptor activation. Thus, augmentation of inhibitory CD47-SIRPalpha signaling may prevent or attenuate RBC clearance in AIHA. |
| Databáze: | OpenAIRE |
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