uPA/uPAR system is active in immature dendritic cells derived from CD14+CD34+ precursors and is down-regulated upon maturation
uPA/uPAR system is active in immature dendritic cells derived from CD14+CD34+ precursors and is down-regulated upon maturation
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DOI：
10.4049/jimmunol.164.2.712
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发表时间：
2000-01-15
影响因子：
4.4
通讯作者：
Zocchi, MR
中科院分区：
文献类型：
--
作者：
Ferrero, E;Vettoretto, K;Zocchi, MR
我们最近描述了能够跨内皮细胞单层迁移并分化为免疫刺激性树突状细胞（DC）的外周CD14（+）CD34（+）细胞子集，在本文中我们表明，源自CD14（+）CD34（+）前体的未成熟DC也能够使用尿激酶纤溶酶原激活剂受体（uPAR）逆转跨内皮迁移和细胞外基质（ECM）侵袭，我们发现这些细胞对巨噬细胞炎症蛋白 (MIP)-1 α 作出反应，增强其侵入 ECM 的能力，并支持未成熟 DC 在炎症部位选择性招募以扩大 APC 池的观点。有趣的是，MIP-1 α 还能够防止通过阻断 uPAR 观察到的基质侵袭减少，表明 uPA/uPAR 系统和 MIP-1 α 合作驱动未成熟 DC 穿过内皮下基质迁移。 TNF-α、CD14(+)CD34(+)来源的DC等刺激可增强其APC功能并降低入侵ECM的能力；这些变化伴随着uPAR表达和功能的改变。此外，成熟的DC将其敏感性从MIP-1α转变为MIP-3β，增强了它们响应后一种趋化因子的跨内皮迁移能力。我们的数据支持这样的假设：血源性 DC 可以通过 ECM 移动到病原体进入位点，在那里它们分化为完全成熟的 APC，其运动和功能受到微环境刺激（包括 MIP-1 α、MIP-3 β 和 TNF-α）的调节。
We recently described a subset of peripheral CD14(+)CD34(+) cells able to migrate across endothelial cell monolayers and differentiate into immunostimulatory dendritic cells (DC), In this paper we show that immature DC derived from CD14(+)CD34(+) precursors are also capable of reverse transendothelial migration and extracellular matrix (ECM) invasion using the urokinase plasminogen activator receptor (uPAR), We found that these cells respond to macrophage-inflammatory protein (MIP)-1 alpha, enhancing their ability to invade ECM and supporting the idea that immature DC are selectively recruited at the site of inflammation to expand the pool of APCs, Interestingly, MIP-1 alpha was also capable of preventing the decreased matrix invasion observed by blocking uPAR, suggesting that the uPA/uPAR system and MIP-1 alpha cooperate in driving immature DC migration through the subendothelial matrix, Upon exposure to maturating stimuli, such as TNF-alpha, CD14(+)CD34(+)-derived DC enhance their APC function and decrease the capacity of invading ECM; these changes are accompanied by altered expression and function of uPAR, Moreover, mature DC shift their sensitivity from MIP-1 alpha to MIP-3 beta, enhancing their transendothelial migration capability in response to the latter chemokine. Our data support the hypothesis that bloodborne DC can move through ECM toward the site of pathogen entry where they differentiate into fully mature APCs with their motility and function regulated by microenvironmental stimuli, including MIP-1 alpha, MIP-3 beta, and TNF-alpha.