Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation.
Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation.
复制标题
DOI：
10.1038/srep44189
复制
发表时间：
2017-03-13
影响因子：
4.6
通讯作者：
Voisin MB
中科院分区：
文献类型：
--
作者：
Arokiasamy S;Zakian C;Dilliway J;Wang W;Nourshargh S;Voisin MB
中性粒细胞被认为在其募集到发炎组织和淋巴器官后在先天性和获得性免疫之间的界面上发挥关键作用。虽然中性粒细胞通过血管的运输已被广泛研究，但调节其迁移到淋巴系统的分子机制仍然知之甚少。在这里，我们已经分析了在真实的时间和在体内使用活体共聚焦显微镜应用于发炎的提睾肌嗜淋巴管的相互作用。我们发现，抗原致敏的组织诱导组织浸润的中性粒细胞进入淋巴管和随后的爬行沿着淋巴管内皮的管腔侧的快速，但短暂的入口。有趣的是，使用TNF受体p55和p75缺陷的小鼠、嵌合动物和抗TNF α抗体阻断，我们证明TNFα的组织释放控制中性粒细胞通过淋巴内皮的迁移和管腔爬行。从机制上讲，我们发现TNFα以严格的CCR 7依赖性方式直接引发中性粒细胞进入淋巴管;并诱导淋巴管上的ICAM-1上调，使中性粒细胞以ICAM-1/MAC-1依赖性方式沿淋巴管内皮腔沿着爬行。总的来说，我们的研究结果证明了TNFα作为体内中性粒细胞进入淋巴系统和在淋巴系统内转运的关键调节剂的新作用。
Neutrophils are recognised to play a pivotal role at the interface between innate and acquired immunities following their recruitment to inflamed tissues and lymphoid organs. While neutrophil trafficking through blood vessels has been extensively studied, the molecular mechanisms regulating their migration into the lymphatic system are still poorly understood. Here, we have analysed neutrophil-lymphatic vessel interactions in real time and in vivo using intravital confocal microscopy applied to inflamed cremaster muscles. We show that antigen sensitisation of the tissues induces a rapid but transient entry of tissue-infiltrated neutrophils into lymphatic vessels and subsequent crawling along the luminal side of the lymphatic endothelium. Interestingly, using mice deficient in both TNF receptors p55 and p75, chimeric animals and anti-TNFα antibody blockade we demonstrate that tissue-release of TNFα governs both neutrophil migration through the lymphatic endothelium and luminal crawling. Mechanistically, we show that TNFα primes directly the neutrophils to enter the lymphatic vessels in a strictly CCR7-dependent manner; and induces ICAM-1 up-regulation on lymphatic vessels, allowing neutrophils to crawl along the lumen of the lymphatic endothelium in an ICAM-1/MAC-1-dependent manner. Collectively, our findings demonstrate a new role for TNFα as a key regulator of neutrophil trafficking into and within lymphatic system in vivo.