Davis T A, Saini A A, Blair P J, Levine B L, Craighead N, Harlan D M, June C H, Lee K P
Immune Cell Biology Program, Stem Cell Biology Branch, Naval Medical Research Institute, Bethesda, MD 20889-5067, USA.
J Immunol. 1998 Apr 15;160(8):3689-97.
The intracellular signals that mediate the differentiation of pluripotent hemopoietic progenitors to dendritic cells (DC) are largely undefined. We have found that the phorbol ester PMA by itself induced 47% +/- 8.7% of input human CD34+ hemopoietic progenitors to differentiate into cells with morphology and surface Ag phenotype characteristic of DC by day 7 of culture. Functionally, PMA-generated DC processed and presented whole soluble Ag and also induced resting T cell proliferation and Ag-specific CTL effector function. Unlike cytokine-driven DC differentiation, PMA suppressed proliferation and induced cell death (in part via apoptosis) in cells that did not differentiate to DC. The effects of PMA were blocked by inhibitors of protein kinase C activation, suggesting a central role for this signaling molecule. PMA-mediated signaling also induced expression of the RelB transcription factor, an NF-kappaB family member implicated in DC differentiation. These findings suggest that phorbol esters activate protein kinase C, which then initiates the terminal component of an intracellular signaling pathway(s) involved in the DC differentiation of CD34+ hemopoietic progenitors.
介导多能造血祖细胞分化为树突状细胞（DC）的细胞内信号在很大程度上尚不清楚。我们发现佛波酯PMA自身就能在培养7天时诱导47%±8.7%的输入人CD34+造血祖细胞分化为具有DC形态和表面抗原表型特征的细胞。在功能上，PMA诱导产生的DC能够处理并呈递全溶性抗原，还能诱导静息T细胞增殖以及抗原特异性CTL效应功能。与细胞因子驱动的DC分化不同，PMA抑制未分化为DC的细胞增殖并诱导细胞死亡（部分通过凋亡）。PMA的作用被蛋白激酶C激活抑制剂所阻断，这表明该信号分子起着核心作用。PMA介导的信号传导还诱导了RelB转录因子的表达，RelB是一种与DC分化有关的NF-κB家族成员。这些发现表明佛波酯激活蛋白激酶C，进而启动参与CD34+造血祖细胞DC分化的细胞内信号通路的终末成分。
