Biogenesis and exocytosis of Weibel-Palade bodies
Biogenesis and exocytosis of Weibel-Palade bodies
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DOI：
10.1007/s00418-001-0368-9
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发表时间：
2002-02-01
影响因子：
2.3
通讯作者：
Voorberg, J
中科院分区：
文献类型：
--
作者：
van Mourik, JA;de Wit, TR;Voorberg, J
血管内皮细胞含有典型的细长囊泡，即所谓的韦伯-帕拉德体，其充当血管性血友病因子（vonWillebrand factor，VWF）的储存室，VWF是一种在控制血管损伤部位血小板粘附和聚集中起重要作用的血浆蛋白。当内皮细胞被激动剂如凝血酶、肾上腺素或组胺激活时，韦伯-帕拉德体与质膜融合并将其内容物释放到血液循环中。这一过程提供了一种适当的手段，通过这种手段，内皮细胞可以积极参与控制血管损伤后的出血停止。除了VWF，韦伯-帕拉德小体还含有其他蛋白质的子集，包括白细胞介素-8（IL-8）、P-选择素和内皮素。与VWF类似，这些蛋白质在刺激时被转运到细胞外，并可控制局部或全身生物学效应，包括炎症和血管活性反应。显然，内皮细胞能够为各种生物活性分子创造一个储存库，这些分子可以根据需要动员。缺乏VWF合成的内皮细胞不仅不能形成韦伯-帕拉德体，而且缺乏储存IL-8或P-选择素或以调节方式释放这些蛋白质的能力。因此，似乎VWF不仅在控制原发性止血中起着重要作用，而且还可以通过其将炎症介质靶向内皮的调节分泌途径的能力来调节炎症过程。
Vascular endothelial cells contain typical, elongated vesicles, the so-called Weibel-Palade bodies, which serve as a storage compartment for von Willebrand factor (VWF), a plasma protein that plays an essential role in controlling the adhesion and aggregation of platelets at sites of vascular injury. Upon activation of endothelial cells by agonists such as thrombin, epinephrine or histamine, the Weibel-Palade bodies fuse with the plasma membrane and release their contents into the blood circulation. This process provides an adequate means by which endothelial cells can actively participate in controlling the arrest of bleeding upon vascular damage. Besides VWF, Weibel-Palade bodies contain a subset of other proteins, including interleukin-8 (IL-8), P-selectin and endothelin. Similar to VWF, these proteins are transported to the outside of the cell upon stimulation and may control local or systemic biological effects, including inflammatory and vasoactive responses. Apparently, endothelial cells are able to create a storage pool for a variety of bioactive molecules which can be mobilised upon demand. Endothelial cells that are deficient of VWF synthesis are not only unable to form Weibel-Palade bodies, but also lack the ability to store IL-8 or P-selectin or release these proteins in a regulated manner. It thus appears that VWF not only plays a prominent role in controlling primary haemostasis, but also may modulate inflammatory processes through its ability to target inflammatory mediators to the regulated secretion pathway of the endothelium.