The Notch ligand, Delta-1, inhibits the differentiation of monocytes into macrophages but permits their differentiation into dendritic cells
The Notch ligand, Delta-1, inhibits the differentiation of monocytes into macrophages but permits their differentiation into dendritic cells
复制标题
DOI：
10.1182/blood.v98.5.1402
复制
发表时间：
2001-09-01
期刊：
影响因子：
20.3
通讯作者：
Bernstein, ID
中科院分区：
文献类型：
--
作者：
Ohishi, K;Varnum-Finney, B;Bernstein, ID
已知Notch介导的细胞相互作用可以调节各种发育系统中的细胞命运决定。之前的一份报告指出，单核细胞表达相对较高量的 Notch-1 和 Notch-2，并且 Notch 配体 Delta-1 Delta(ext-myc)) 的固定化胞外结构域会诱导用巨噬细胞集落刺激因子 (M-CSF) 培养的外周血单核细胞凋亡，但不会诱导粒细胞-巨噬细胞 CSF 凋亡 (GM-CSF)。本研究确定了 Notch 信号传导对单核细胞分化为巨噬细胞和树突状细胞的影响。结果显示，固定化Deltaext-myc与GM-CSF一起抑制单核细胞向成熟巨噬细胞(CD1a(+/-)CD14(+/-)CD64(+))的分化。然而，Deltaext-myc 允许使用 GMCSF 和白细胞介素 4 (IL-4) 分化为未成熟树突状细胞 (CD1a(+)CD14(-)CD64(-))，并使用 GM-CSF、IL-4 和肿瘤坏死因子-α 进一步分化为成熟树突状细胞 (CD1a(+)CD83(+)) （肿瘤坏死因子-α）。 Notch信号影响体外CD34(+)细胞衍生的CD1a(-)CD14(+)巨噬细胞/树突状细胞前体的分化。对于 GM-CSF 和 TNF-α，接触 Delta(ext-myc) 会增加分化为 CD1a(+)CD14(-) 树突状细胞的前体细胞比例（Delta(ext-myc) 存在时为 51%，对照培养物中为 10%），而分化为 CD1a(-)CD14(+) 巨噬细胞的比例则下降（Delta(ext-myc) 存在时为 6%，对照培养物中为 10%）。 65%）。这些数据表明Notch信号传导在双能巨噬细胞/树突状前体调节细胞命运决定中的作用。 (C) 2001 年，美国血液学会。
Notch-mediated cellular interactions are known to regulate cell fate decisions In various developmental systems. A previous report Indicated that monocytes express relatively high amounts of Notch-1 and Notch-2 and that the Immobilized extracellular domain of the Notch ligand, Delta-1 Delta(ext-myc)), induces apoptosis in peripheral blood monocytes cultured with macrophage colony-stimulating factor (M-CSF), but not granulocyte-macrophage CSF (GM-CSF). The present study determined the effect of Notch signaling on monocyte differentiation into macrophages and dendritic cells. Re-suits showed that immobilized Deltaext-myc Inhibited differentiation of monocytes into mature macrophages (CD1a(+/-)CD14(+/-)CD64(+)) with GM-CSF. However, Deltaext-myc permitted differentiation into immature dendritic cells (CD1a(+)CD14(-)CD64(-)) with GMCSF and interleukin 4 (IL-4), and further differentiation into mature dendritic cells (CD1a(+)CD83(+)) with GM-CSF, IL-4, and tumor necrosis factor-alpha (TNF-alpha). Notch signaling affected the differentiation of CD1a(-)CD14(+) macrophage/dendritic cell precursors derived in vitro from CD34(+) cells. With GM-CSF and TNF-alpha, exposure to Delta(ext-myc) increased the proportion of precursors that differentiated into CD1a(+)CD14(-) dendritic cells (51% in the presence of Delta(ext-myc) versus 10% in control cultures), whereas a decreased proportion differentiated into CD1a(-)CD14(+) macrophages (6% versus 65%). These data Indicate a role for Notch signaling in regulating cell fate decisions by bipotent macrophage/dendritic precursors. (C) 2001 by The American Society of Hematology.