Oldenborg P A, Gresham H D, Lindberg F P
Division of Infectious Diseases, Department of Internal Medicine and Department of Molecular Microbiology and Pathogenesis, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Exp Med. 2001 Apr 2;193(7):855-62. doi: 10.1084/jem.193.7.855.
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.
在自身免疫性溶血性贫血（AIHA）中，被自身抗体调理的循环红细胞（RBC）被巨噬细胞的Fcγ和补体受体识别。这触发了吞噬作用，并导致脾脏巨噬细胞将红细胞从循环中清除。我们最近发现，未被调理的红细胞上的CD47与巨噬细胞信号调节蛋白α（SIRPα）结合，产生一个负信号，阻止未被调理的红细胞被吞噬。我们在此表明，被调理的红细胞的清除和吞噬作用也受CD47-SIRPα调节。在仅含有残余含Src同源2结构域蛋白酪氨酸磷酸酶（SHP）-1活性的小鼠中，CD47-SIRPα相互作用产生的抑制作用虽大幅减弱但并未完全消失，这表明该系统中大多数SIRPα信号传导是由SHP-1磷酸酶活性介导的。巨噬细胞的吞噬反应受抑制性SIRPα信号与促吞噬信号（如来自Fcγ和补体受体激活的信号）整合的控制。因此，增强抑制性CD47-SIRPα信号传导可能预防或减轻AIHA中的红细胞清除。
