Inhibition of lymphangiogenesis and lymphatic drainage via vascular endothelial growth factor receptor 3 blockade increases the severity of inflammation in a mouse model of chronic inflammatory arthritis.

Inhibition of lymphangiogenesis and lymphatic drainage via vascular endothelial growth factor receptor 3 blockade increases the severity of inflammation in a mouse model of chronic inflammatory arthritis.
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在慢性炎性关节炎的小鼠模型中,通过血管内皮生长因子受体3封锁抑制淋巴管生成和淋巴引流会增加炎症的严重程度。

DOI:
10.1002/art.24764
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发表时间:
2009-09
影响因子:
--
通讯作者:
Xing, Lianping
Xing, Lianping
中科院分区:
其他
文献类型:
--
作者:
Guo, Ruolin;Zhou, Quan;Proulx, Steven T.;Wood, Ronald;Ji, Rui-Cheng;Ritchlin, Christopher T.;Pytowski, Bronislaw;Zhu, Zhenping;Wang, Yong-Jun;Schwarz, Edward M.;Xing, Lianping

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研究小鼠关节炎进展过程中淋巴抑制对关节和引流淋巴结病理学的影响。TNF转基因(TNF-Tg)小鼠用作慢性炎性关节炎的模型。在用VEGFR-3或VEGFR-2中和抗体或同种型IgG治疗之前和之后8周,小鼠接受对比增强MRI以获得踝关节和膝关节滑膜体积和引流腘淋巴结(PLN)体积。在处死前,对动物进行近红外淋巴成像,以确定VEGFR-3中和对淋巴从爪子转运到引流淋巴结的影响。通过组织学、免疫组织化学和RT-PCR检测关节和淋巴结的淋巴管形成和形态。与IgG治疗相比,VEGFR-3中和抗体治疗显著降低了PLN的大小、关节和PLN中的淋巴管数量、从爪到PLN的淋巴引流以及PLN中表达VEGF-C的CD 11b+骨髓细胞的数量。但是,它增加了踝关节和膝关节的滑膜体积和炎症面积。相比之下,VEGFR-2中和抗体抑制淋巴管生成和关节炎症。在慢性关节炎的发展过程中,淋巴管生成和淋巴引流与关节病变的严重程度密切相关。淋巴引流在控制慢性炎症的进展中起着有益的作用。
Investigation of the effect of lymphatic inhibition on joint and draining lymph node pathology during the course of arthritis progression in mice. TNF transgenic (TNF-Tg) mice were used as a model of chronic inflammatory arthritis. Mice received contrast enhanced MRI to obtain ankle and knee joint synovial volumes and draining popliteal lymph node (PLN) volumes before and 8 weeks after treatment with VEGFR-3 or VEGFR-2 neutralizing antibodies, or isotype IgG. The animals were subjected to near-infrared lymphatic imaging to determine the effect of VEGFR-3 neutralization on lymph transport from paws to draining PLNs prior to sacrifice. Lymphatic vessel formation and morphology of joints and PLNs were examined by histology, immunohistochemistry, and RT-PCR. Compared to IgG treatment, VEGFR-3 neutralizing antibody treatment significantly decreased the size of PLNs, the number of lymphatic vessels in joints and PLNs, the lymphatic drainage from paws to PLNs, and the number of VEGF-C expressing CD11b+ myeloid cells in PLNs. However, it increased the synovial volumes and inflammatory area in ankle and knee joints. VEGFR-2 neutralizing antibody, in contrast, inhibited both lymphangiogenesis and joint inflammation. Lymphangiogenesis and lymphatic drainage are reciprocally related to the severity of joint lesions during the development of chronic arthritis. Lymphatic drainage plays a beneficial role in controlling the progression of chronic inflammation.
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发表时间: 2007-01-01
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