Kanbe E, Emi N, Abe A, Tanaka H, Kobayashi K, Saito H
First Department of Internal Medicine, Graduate School of Medicine, Nagoya University, Japan.
Int J Hematol. 2001 Oct;74(3):309-15. doi: 10.1007/BF02982066.
Macrophage mannose receptor (MMR) recognizes the pattern of carbohydrates exposed on microorganisms and mediates endocytosis in macrophages. We have synthesized glycoconjugate cationic polymers carrying 3,6-branched alpha-D-mannoside, a trimannose conjugate (TMC) with a high affinity for mannose-specific lectins. Culture with 10 microM TMC for 6 hours induced adhesion and aggregation in NKM-1, a human myelomonocytic leukemia cell line. TMC also stimulated the accumulation of fluorescein isothiocyanate (FITC)-dextran (FITC-DX). This accumulation seemed to be mediated by endocytosis via MMR because mannan, which specifically binds to MMR, inhibited FITC-DX accumulation. Expression of CD14, adhesion molecules, and costimulatory molecules was induced for 24 hours in NKM-1 and in fresh leukemia blasts from 4 patients with acute myeloid leukemia (AML) M4 and M5 subtypes (French-American-British classification). To clarify the binding mechanism, we compared mannose conjugates and a monomer of mannose regarding their effects on endocytosis and enhancement of CD14 and CD86 expression. A polymer of monomannose clusters with a lower affinity for lectins slightly stimulated exdocytosis, whereas a monomer of trimannose had no effect. These findings suggest that concatenation between MMR and TMC may play an important role in the activation of monocytic leukemia cells. TMC may become a good candidate to target MMRs of leukemia cells.
巨噬细胞甘露糖受体（MMR）可识别微生物表面暴露的碳水化合物模式，并介导巨噬细胞的内吞作用。我们合成了携带3,6-分支α-D-甘露糖苷的糖缀合物阳离子聚合物，这是一种对甘露糖特异性凝集素具有高亲和力的三甘露糖缀合物（TMC）。用10μM TMC培养6小时可诱导人骨髓单核细胞白血病细胞系NKM-1发生黏附和聚集。TMC还刺激了异硫氰酸荧光素（FITC）-葡聚糖（FITC-DX）的积累。这种积累似乎是通过MMR介导的内吞作用实现的，因为特异性结合MMR的甘露聚糖抑制了FITC-DX的积累。在NKM-1以及4例急性髓系白血病（AML）M4和M5亚型（法美英分类法）患者的新鲜白血病原始细胞中，CD14、黏附分子和共刺激分子的表达被诱导了24小时。为了阐明结合机制，我们比较了甘露糖缀合物和甘露糖单体对内吞作用以及CD14和CD86表达增强的影响。对凝集素亲和力较低的单甘露糖簇聚合物轻微刺激了胞吐作用，而三甘露糖单体则没有作用。这些发现表明，MMR与TMC之间的连接可能在单核细胞白血病细胞的激活中起重要作用。TMC可能成为靶向白血病细胞MMR的良好候选物。
