Dysmorphogenesis of lymph nodes in Foxc2 haploinsufficient mice
Dysmorphogenesis of lymph nodes in Foxc2 haploinsufficient mice
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DOI：
10.1007/s00418-011-0819-x
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发表时间：
2011-05
影响因子：
2.3
通讯作者：
H. Shimoda;M. Bernas;M. Witte
中科院分区：
文献类型：
--
作者：
H. Shimoda;M. Bernas;M. Witte
通过免疫组织化学和电子显微镜研究了叉头转录因子Foxc 2单倍不足小鼠淋巴结的异常形态发生，该小鼠是一种水肿-双列吸虫病综合征模型。Foxc 2杂合小鼠表现出淋巴结增生，包括形成淋巴窦的内皮细胞明显增生和淋巴髓中（特别是窦周围）的α-平滑肌肌动蛋白（SMA）免疫阳性成纤维细胞样细胞。增生的窦内皮细胞和SMA阳性细胞分别显示血小板衍生生长因子（PDGF）-B（血管壁细胞募集的关键化学引诱物）及其受体PDGFR-β的不同免疫定位。这些观察结果表明，静脉窦内皮细胞通过PDGF-B/PDGFR-β信号在Foxc 2杂合子的淋巴结中引起成纤维细胞样细胞作为一种血管壁细胞的异常募集。此外，在Foxc 2杂合子淋巴结中，募集的SMA阳性细胞显示出对血管内皮生长因子（VEGF）-C的强烈免疫反应，VEGF-C是一种高度特异性的淋巴管生成因子，其受体VEGFR-3优先分布在淋巴窦内皮细胞中。这些结果表明，淋巴窦内皮细胞和成纤维细胞样细胞之间的相互作用循环，涉及PDGF-B/PDGFR-β和VEGF-C/VEGFR-3信号传导，是Foxc 2单倍不足中淋巴窦和成纤维细胞样细胞异常增生所必需的。
Dysmorphogenesis of lymph nodes displayed in a fork head transcription factor Foxc2 haploinsufficient mice—a model for lymphedema-distichiasis syndrome—was studied by immunohistochemistry and electron microscopy. TheFoxc2heterozygous mice manifested lymph node hyperplasia composed of conspicuous proliferation of endothelial cells forming the lymphatic sinus and α-smooth muscle actin (SMA)-immunopositive fibroblast-like cells in the lymphatic pulp, particularly around the sinus. The hyperplastic sinus endothelial cells and the SMA-positive cells demonstrated distinct immunolocalization of platelet-derived growth factor (PDGF)-B, a crucial chemoattractant for vascular mural cell recruitment, and its receptor, PDGFR-β, respectively. The observations suggest that the sinus endothelial cells elicit abnormal recruitment of the fibroblast-like cells as a type of vascular mural cells via PDGF-B/PDGFR-β signaling in lymph nodes of theFoxc2heterozygotes. Furthermore, inFoxc2heterozygous lymph nodes, recruited SMA-positive cells displayed an intense immunoreaction for vascular endothelial growth factor (VEGF)-C, a highly specific lymphangiogenic factor, and its receptor, VEGFR-3, was preferentially distributed in the lymphatic sinus endothelial cells. These findings suggest that an interactive cycle between lymphatic sinus endothelial cells and the fibroblast-like cells, which involves PDGF-B/PDGFR-β and VEGF-C/VEGFR-3 signaling, is essential for aberrant hyperplasia of the lymphatic sinus and the fibroblast-like cells in Foxc2 haploinsufficiency.