Plasticity of Button-Like Junctions in the Endothelium of Airway Lymphatics in Development and Inflammation
Plasticity of Button-Like Junctions in the Endothelium of Airway Lymphatics in Development and Inflammation
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DOI：
10.1016/j.ajpath.2012.02.019
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发表时间：
2012-06-01
影响因子：
6
通讯作者：
McDonald, Donald M.
中科院分区：
文献类型：
--
作者：
Yao, Li-Chin;Baluk, Peter;McDonald, Donald M.
与集合血管和血管的连续拉链状连接（拉链）不同，初始血管的内皮细胞具有不连续的纽扣状连接（纽扣）。动脉被认为是液体和细胞进入动脉的主要阀门。为了了解纽扣在发育过程中何时以及如何形成，以及它们是否在疾病中发生变化，我们研究了小鼠胚胎中纽扣的外观及其在持续炎症中的可塑性。我们发现，在胚胎（E）12.5天的淋巴囊和气管上皮细胞在E16.5连接拉链，而不是按钮。然而，随着纽扣的出现，在出生前，拉链在最初的发育过程中迅速减少。纽扣的比例从E17.5时的6%和E18.5时的12%增加到出生时的35%，出生后第7天（P）的50%，P28的90%和P70的100%。在炎症中，在呼吸道支原体感染后14天和28天，拉链取代了气道内的纽扣。淋巴结的变化被地塞米松逆转，但不能被抗体mF 4 - 31 C1抑制血管内皮生长因子受体-3信号传导逆转。地塞米松还通过淋巴管内皮细胞中糖皮质激素受体磷酸化的直接作用促进出生后早期发育过程中的纽扣形成。这些发现证明了在发育和炎症过程中淋巴管细胞间连接的可塑性，并表明淋巴管内皮细胞中糖皮质激素受体信号传导可以促进按钮形成。(Am J Pathol 2012，180：2561-2575; http：//dx.doi.org/10.1016/j.ajpath.2012.02.019）
Endothelial cells of initial lymphatics have discontinuous button-like junctions (buttons), unlike continuous zipper-like junctions (zippers) of collecting lymphatics and blood vessels. Buttons are thought to act as primary valves for fluid and cell entry into lymphatics. To learn when and how buttons form during development and whether they change in disease, we examined the appearance of buttons in mouse embryos and their plasticity in sustained inflammation. We found that endothelial cells of lymph sacs at embryonic day (E)12.5 and tracheal lymphatics at E16.5 were joined by zippers, not buttons. However, zippers in initial lymphatics decreased rapidly just before birth, as buttons appeared. The proportion of buttons increased from only 6% at E17.5 and 12% at E18.5 to 35% at birth, 50% at postnatal day (P)7, 90% at P28, and 100% at P70. In inflammation, zippers replaced buttons in airway lymphatics at 14 and 28 days after Mycoplasma pulmonis infection of the respiratory tract. The change in lymphatic junctions was reversed by dexamethasone but not by inhibition of vascular endothelial growth factor receptor-3 signaling by antibody mF4-31C1. Dexamethasone also promoted button formation during early postnatal development through a direct effect involving glucocorticoid receptor phosphorylation in lymphatic endothelial cells. These findings demonstrate the plasticity of intercellular junctions in lymphatics during development and inflammation and show that button formation can be promoted by glucocorticoid receptor signaling in lymphatic endothelial cells. (Am J Pathol 2012, 180:2561-2575; http://dx.doi.org/10.1016/j.ajpath.2012.02.019)