Jaiswal Siddhartha, Jamieson Catriona H M, Pang Wendy W, Park Christopher Y, Chao Mark P, Majeti Ravindra, Traver David, van Rooijen Nico, Weissman Irving L
Ludwig Center at Stanford, Stanford Cancer Center, Department of Pathology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell. 2009 Jul 23;138(2):271-85. doi: 10.1016/j.cell.2009.05.046.
Macrophages clear pathogens and damaged or aged cells from the blood stream via phagocytosis. Cell-surface CD47 interacts with its receptor on macrophages, SIRPalpha, to inhibit phagocytosis of normal, healthy cells. We find that mobilizing cytokines and inflammatory stimuli cause CD47 to be transiently upregulated on mouse hematopoietic stem cells (HSCs) and progenitors just prior to and during their migratory phase, and that the level of CD47 on these cells determines the probability that they are engulfed in vivo. CD47 is also constitutively upregulated on mouse and human myeloid leukemias, and overexpression of CD47 on a myeloid leukemia line increases its pathogenicity by allowing it to evade phagocytosis. We conclude that CD47 upregulation is an important mechanism that provides protection to normal HSCs during inflammation-mediated mobilization, and that leukemic progenitors co-opt this ability in order to evade macrophage killing.
巨噬细胞通过吞噬作用清除血流中的病原体以及受损或衰老的细胞。细胞表面的CD47与巨噬细胞上的受体信号调节蛋白α（SIRPα）相互作用，以抑制对正常健康细胞的吞噬作用。我们发现，动员细胞因子和炎性刺激会使小鼠造血干细胞（HSC）及其祖细胞在迁移阶段之前和期间短暂上调CD47，并且这些细胞上CD47的水平决定了它们在体内被吞噬的可能性。在小鼠和人类髓系白血病中，CD47也会持续上调，并且在髓系白血病细胞系上过度表达CD47会通过使其逃避吞噬作用而增加其致病性。我们得出结论，CD47上调是一种重要机制，在炎症介导的动员过程中为正常造血干细胞提供保护，并且白血病祖细胞利用这种能力来逃避巨噬细胞的杀伤。
