Lung vascular endothelial growth factor expression induces local myeloid dendritic cell activation
Lung vascular endothelial growth factor expression induces local myeloid dendritic cell activation
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DOI：
10.1016/j.clim.2009.05.016
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发表时间：
2009-09-01
影响因子：
8.6
通讯作者：
Elias, Jack A.
中科院分区：
文献类型：
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作者：
Chapoval, Svetlana P.;Lee, Chun Geun;Elias, Jack A.
我们以前证明，血管内皮生长因子（VEGF）在小鼠肺表达增加局部CD 11 c +MHCII+ DC的数量和激活。在这项研究中，采用流式细胞术，我们报告了增加的髓样（mDC）和浆细胞样（pDC）的VEGF转基因小鼠（tg）的肺相比，野生型小鼠。来自VEGF tg小鼠的肺pDC表现出更高水平的活化，MHCII和共刺激分子的表达增加。由于VEGF tg小鼠显示哮喘样表型，并且肺mDC在哮喘环境中起关键作用，因此进行研究以进一步表征鼠肺mDC。与从WT对照小鼠获得的那些相比，来自VEGF tg肺的分选的mDC的评估证明了组织蛋白酶K、MMP-8、MMP-9、MMP-12和MMP-14以及趋化因子受体的选择性上调。它们也增加了VEGFR 2，但下调了VEGFR 1的表达。这些细胞中的趋化因子和调节性细胞因子表达的分析显示巨噬细胞趋化蛋白-3（MCP-3）、胸腺表达的趋化因子（TECK）、次级淋巴器官趋化因子（SLC）、巨噬细胞衍生的趋化因子（MDC）、IL-1 β、IL-6、IL-12和IL-13的上调。与WT小鼠相比，VEGF tg小鼠肺DC的抗原（Ag）OVA-FITC摄取和载Ag DC向局部淋巴结的迁移显著增加。因此，VEGF可能通过激活局部DC使肺易于炎症和/或修复。它调节先天免疫效应分子的肺mDC表达。本文提供的数据表明肺VEGF表达如何在功能上影响局部mDC从先天性应答向Th 2型炎症应答的转变。(C)2009 Elsevier Inc. All rights reserved.
We previously demonstrated that vascular endothelial growth factor (VEGF) expression in the murine lung increases local CD11c+MHCII+ DC number and activation. In this study, employing a multicolor flow cytometry, we report increases in both myeloid (mDC) and plasmacytoid (pDC) DC in the lungs of VEGF transgenic (tg) compared to WT mice. Lung pDC from VEGF tg mice exhibited higher levels of activation with increased expression of MHCII and costimulatory molecules. As VEGF tg mice display an asthma-like phenotype and lung mDC play a critical role in asthmatic setting, studies were undertaken to further characterize murine lung mDC. Evaluations of sorted mDC from VEGF tg lungs demonstrated a selective upregulation of cathepsin K, MMP-8, -9, -12, and -14, and chemokine receptors as compared to those obtained from WT control mice. They also had increased VEGFR2 but downregulated VEGFR1 expression. Analysis of chemokine and regulatory cytokine expression in these cells showed an upregulation of macrophage chemotactic protein-3 (MCP-3), thymus-expressed chemokine (TECK), secondary lymphoid organ chemokine (SLC), macrophage-derived chemokine (MDC),IL-1 beta, IL-6, IL-12 and IL-13. The antigen (Ag) OVA-FITC uptake by lung DC and the migration of Ag-loaded DC to local lymph nodes were significantly increased in VEGF tg mice compared to WT mice. Thus, VEGF may predispose the lung to inflammation and/or repair by activating local DC. It regulates lung mDC expression of innate immunity effector molecules. The data presented here demonstrate how lung VEGF expression functionally affects local mDC for the transition from the innate response to a Th2-type inflammatory response. (C) 2009 Elsevier Inc. All rights reserved.