Treatment of Tumor Necrosis Factor-Transgenic Mice With Anti-Tumor Necrosis Factor Restores Lymphatic Contractions, Repairs Lymphatic Vessels, and May Increase Monocyte/Macrophage Egress
Treatment of Tumor Necrosis Factor-Transgenic Mice With Anti-Tumor Necrosis Factor Restores Lymphatic Contractions, Repairs Lymphatic Vessels, and May Increase Monocyte/Macrophage Egress
复制标题
DOI：
10.1002/art.40047
复制
发表时间：
2017-06-01
影响因子：
13.3
通讯作者：
Schwarz, Edward M.
中科院分区：
文献类型：
--
作者：
Bouta, Echoe M.;Kuzin, Igor;Schwarz, Edward M.
目的最近的研究表明，受影响关节的淋巴流出与炎症性关节炎之间存在负相关关系。作为模型，肿瘤坏死因子（TNF）转基因小鼠在引流淋巴结（LN）塌陷和发炎关节下游淋巴收缩丧失后出现晚期关节炎。目前尚不清楚这些淋巴缺陷是否可逆。本研究的目的是检验抗 TNF 疗法可减少晚期糜烂性炎症关节炎的假设，该关节炎与淋巴管收缩的恢复、受损淋巴管的修复以及单核细胞排出增加的证据有关。方法用抗 TNF 单克隆抗体（每周 10 mg/kg）或安慰剂治疗患有晚期关节炎和腘淋巴结塌陷的 TNF 转基因小鼠 6 周，观察对膝关节滑膜炎、淋巴管超微结构和功能以及腘淋巴结的影响通过超声、组织学、透射电子显微镜 (TEM)、近红外吲哚菁绿成像和流式细胞术评估细胞结构。结果抗 TNF 治疗显着减少滑膜炎（约 5 倍；P
ObjectiveRecent studies have demonstrated that there is an inverse relationship between lymphatic egress and inflammatory arthritis in affected joints. As a model, tumor necrosis factor (TNF)-transgenic mice develop advanced arthritis following draining lymph node (LN) collapse, and loss of lymphatic contractions downstream of inflamed joints. It is unknown if these lymphatic deficits are reversible. This study was undertaken to test the hypothesis that anti-TNF therapy reduces advanced erosive inflammatory arthritis, associated with restoration of lymphatic contractions, repair of damaged lymphatic vessels, and evidence of increased monocyte egress.MethodsTNF-transgenic mice with advanced arthritis and collapsed popliteal LNs were treated with anti-TNF monoclonal antibody (10 mg/kg weekly) or placebo for 6 weeks, and effects on knee synovitis, lymphatic vessel ultrastructure and function, and popliteal LN cellularity were assessed by ultrasound, histology, transmission electron microscopy (TEM), near-infrared indocyanine green imaging, and flow cytometry.ResultsAnti-TNF therapy significantly decreased synovitis (approximate to 5-fold; P