Colonic Insult Impairs Lymph Flow, Increases Cellular Content of the Lymph, Alters Local Lymphatic Microenvironment, and Leads to Sustained Inflammation in the Rat Ileum.
Colonic Insult Impairs Lymph Flow, Increases Cellular Content of the Lymph, Alters Local Lymphatic Microenvironment, and Leads to Sustained Inflammation in the Rat Ileum.
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DOI：
10.1097/mib.0000000000000402
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发表时间：
2015-07
影响因子：
4.9
通讯作者：
Zawieja DC
中科院分区：
文献类型：
--
作者：
Cromer W;Wang W;Zawieja SD;von der Weid PY;Newell-Rogers MK;Zawieja DC
自 20 世纪 30 年代以来，淋巴功能障碍一直与炎症有关。尽管在早期 IBD 模型中使用了淋巴管阻塞，但在 IBD 模型中，肠道和肠系膜的淋巴功能尚未得到充分研究。先天性和适应性免疫系统的激活是 TNBS 诱导的炎症的标志，并且与内在淋巴泵的破坏有关。最近对淋巴管驻留免疫细胞之间的串扰和淋巴管收缩性调节的识别强调了在组织炎症响应 TNBS 期间淋巴功能障碍时机的重要性。为了评估 TNBS 诱导的炎症中的淋巴功能，收集肠系膜淋巴管的淋巴液并测量流量。还测量了淋巴的细胞结构和细胞因子谱。进行组织病理学以确定损伤的严重程度，并对肠系膜进行免疫荧光染色以评估胃肠道集合淋巴管附近和上的免疫细胞群的变化。 TNBS 给药后 24 小时，淋巴运输下降，72 小时开始恢复。淋巴流量显着减少先于组织病理学评分显着增加，并且与 MPO 活性增加同时发生。在这些变化之前，肠系膜淋巴管周围的 MHCII+ 细胞增加，导致淋巴环境改变，有利于功能障碍。影响淋巴功能的环境因素的变化发生在大体胃肠道炎症发生之前。 TNBS 介导的炎症中淋巴功能的降低可能是损伤发生的早期因素，功能的恢复与炎症的消退相关。
Lymphatic dysfunction has been linked to inflammation since the 1930’s. Lymphatic function in the gut and mesentery is grossly underexplored in models of IBD despite the use of lymphatic occlusion in early models of IBD. Activation of the innate and adaptive immune system is a hallmark of TNBS-induced inflammation and is linked to disruption of the intrinsic lymph pump. Recent identification of crosstalk between lymphatic vessel resident immune cells and regulation of lymphatic vessel contractility underscore the importance of the timing of lymphatic dysfunction during tissue inflammation in response to TNBS. To evaluate lymphatic function in TNBS induced inflammation, lymph was collected and flow measured from mesenteric lymphatics. Cellularity and cytokine profile of the lymph was also measured. Histopathology was performed to determine severity of injury and immunofluorescent staining of the mesentery was done to evaluate changes in the population of immune cells that reside near and on gastro-intestinal collecting lymphatics. Lymph transport fell 24hrs after TNBS administration and began recovering at 72hrs. Significant reduction of lymph flow preceded significant increase in histopathological score and occurred simultaneously with increased MPO activity. These changes were preceded by increased MHCII+ cells surrounding mesenteric lymphatics leading to an altered lymphatic environment that would favor dysfunction. Alterations in environmental factors that effect lymphatic function occur before the development of gross GI inflammation. Reduced lymphatic function in TNBS-mediated inflammation is likely an early factor in the development of injury and that recovery of function is associated with resolution of inflammation.