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Original Article |
(Sirp
) Regulates Fc
and Complement Receptor–Mediated Phagocytosis
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
, signal regulatory protein
. © 2001 The Rockefeller University Press
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