Relationships Between Lymphangiogenesis and Angiogenesis During Inflammation in Rat Mesentery Microvascular Networks

Relationships Between Lymphangiogenesis and Angiogenesis During Inflammation in Rat Mesentery Microvascular Networks
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DOI:
10.1089/lrb.2012.0014
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发表时间:
2012-01-01
影响因子:
1.4
通讯作者:
Murfee, Walter L.
Murfee, Walter L.
中科院分区:
医学4区
文献类型:
--
作者:
Sweat, Richard S.;Stapor, Peter C.;Murfee, Walter L.

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背景资料:淋巴和血液微血管系统在炎症期间调节间质液平衡和免疫细胞运输中发挥协调作用。本研究的目的是表征淋巴管和血管生长在成年大鼠肠系膜炎症stimulation.Methods和结果:肠系膜组织收获未经刺激的成年雄性Wistar大鼠和在3,10和30天后化合物48/80刺激的时间和空间之间的关系。对组织进行PECAM、LYVE-1、Prox 1、podoplanin、CD 11b和III类β-微管蛋白的免疫标记。每个时间点定量每个血管系统的血管面积、毛细血管盲端密度和血管长度密度。到第10天,与未刺激的组织相比,血管面积增加,并且在第30天保持增加。在第3天毛细血管出芽达到高峰后,血管面积和密度在第10天增加。盲端淋巴管的数量和淋巴密度直到第10天才显著增加,并且与未刺激的水平相比,淋巴管面积直到第30天才增加。淋巴管生成与沿着淋巴盲端血管的内皮细胞上调III类b-微管蛋白表达和增加淋巴/血液内皮细胞连接相关。在局部组织区域包含血液和淋巴管,存在的血管生成衰减毛细血管sprouting.Conclusions:我们的工作表明,淋巴管生成滞后于炎症过程中的血管生成,并激发了未来的调查,旨在了解淋巴/血液内皮细胞的相互作用的需要。结果还表明,淋巴管内皮细胞在淋巴管生成过程中发生表型变化。
Background: Lymphatic and blood microvascular systems play a coordinated role in the regulation of interstitial fluid balance and immune cell trafficking during inflammation. The objective of this study was to characterize the temporal and spatial relationships between lymphatic and blood vessel growth in the adult rat mesentery following an inflammatory stimulus.Methods and Results: Mesenteric tissues were harvested from unstimulated adult male Wistar rats and at 3, 10, and 30 days post compound 48/80 stimulation. Tissues were immunolabeled for PECAM, LYVE-1, Prox1, podoplanin, CD11b, and class III beta-tubulin. Vascular area, capillary blind end density, and vascular length density were quantified for each vessel system per time point. Blood vascular area increased compared to unstimulated tissues by day 10 and remained increased at day 30. Following the peak in blood capillary sprouting at day 3, blood vascular area and density increased at day 10. The number of blind-ended lymphatic vessels and lymphatic density did not significantly increase until day 10, and lymphatic vascular area was not increased compared to the unstimulated level until day 30. Lymphangiogenesis correlated with the upregulation of class III b-tubulin expression by endothelial cells along lymphatic blind-ended vessels and increased lymphatic/blood endothelial cell connections. In local tissue regions containing both blood and lymphatic vessels, the presence of lymphatics attenuated blood capillary sprouting.Conclusions: Our work suggests that lymphangiogenesis lags angiogenesis during inflammation and motivates the need for future investigations aimed at understanding lymphatic/blood endothelial cell interactions. The results also indicate that lymphatic endothelial cells undergo phenotypic changes during lymphangiogenesis.