Bächli Esther B, Schaer Dominik J, Walter Roland B, Fehr Jörg, Schoedon Gabriele
Department of Medicine, University Hospital of Zürich, CH-8091 Zürich, Switzerland.
J Leukoc Biol. 2006 Feb;79(2):312-8. doi: 10.1189/jlb.0605309. Epub 2005 Dec 20.
The hemoglobin-haptoglobin (Hb-Hp) scavenger receptor CD163 is a monocyte/macrophage-restricted surface antigen, whose expression is strongly up-regulated by glucocorticoids. We have previously shown that CD163 is expressed by acute myeloid leukemia (AML) cells of monocytic lineage. Herein, we expand this finding by demonstrating constitutive and glucocorticoid-enhanced CD163 expression on French-American-British M4/M5 AML cells, and leukemic blasts of other AML subtypes and normal hematopoietic progenitor cells do not express CD163. We provide evidence that the functional characteristics of CD163 are preserved on malignant cells by showing the capability of types M4/M5 blast cells to internalize Hb-Hp by a CD163-mediated mechanism. Together, our results identify CD163 as a potential target for therapeutic intervention. It is important that CD163 does not appear to be released from leukemic blasts under noninflammatory conditions, thus reducing the probability of off-target side-effects as a result of competitive binding of potential therapeutic ligands to nonmembrane-bound CD163.
血红蛋白-触珠蛋白(Hb-Hp)清除受体CD163是一种单核细胞/巨噬细胞限制性表面抗原,其表达受糖皮质激素强烈上调。我们之前已表明,CD163在单核细胞系急性髓系白血病(AML)细胞中表达。在此,我们通过证明法美英协作组(FAB)M4/M5型AML细胞、其他AML亚型的白血病原始细胞以及正常造血祖细胞上组成性和糖皮质激素增强的CD163表达,扩展了这一发现,且正常造血祖细胞不表达CD163。我们通过展示M4/M5型原始细胞通过CD163介导的机制内化Hb-Hp的能力,提供了CD163在恶性细胞上功能特性得以保留的证据。总之,我们的结果确定CD163为治疗干预的潜在靶点。重要的是,在非炎症条件下,CD163似乎不会从白血病原始细胞中释放,从而降低了潜在治疗配体与非膜结合CD163竞争性结合导致脱靶副作用的可能性。