Wolff B, Burns A R, Middleton J, Rot A
Novartis Forschungsinstitut, A-1235 Vienna, Austria.
J Exp Med. 1998 Nov 2;188(9):1757-62. doi: 10.1084/jem.188.9.1757.
The expression and secretion of interleukin (IL)-8, the prototype member of the C-X-C subfamily of chemokines, can be induced by diverse inflammatory stimuli in many cells, including endothelial cells (EC). Upon de novo synthesis, IL-8 localizes intracellularly in the Golgi apparatus, from where it is secreted. In addition to this constitutive secretory pathway, we describe a depot storage and separate regulated secretory pathway of IL-8 in EC. The prolonged stimulation of primary human EC with inflammatory mediators resulted in the accumulation of IL-8 in Weibel-Palade bodies, where it colocalized with von Willebrand factor. IL-8 was retained in these storage organelles for several days after the removal of the stimulus and could be released by EC secretagogues such as phorbol myristate acetate, the calcium ionophore A23187, and histamine. These findings suggest that storage of IL-8 in Weibel-Palade bodies may serve as the EC "memory" of a preceding inflammatory insult, which then enables the cells to secrete IL-8 immediately without de novo protein synthesis.
白细胞介素（IL）-8是趋化因子C-X-C亚家族的原型成员，其表达和分泌可由多种炎症刺激在包括内皮细胞（EC）在内的许多细胞中诱导产生。IL-8在重新合成后定位于细胞内的高尔基体，从那里分泌出来。除了这种组成型分泌途径外，我们还描述了EC中IL-8的一种储存库储存和独立调节的分泌途径。用炎症介质对原代人EC进行长时间刺激导致IL-8在魏尔-帕拉德小体中积累，在那里它与血管性血友病因子共定位。在去除刺激后，IL-8在这些储存细胞器中保留了几天，并可被EC促分泌剂如佛波酯肉豆蔻酸酯、钙离子载体A23187和组胺释放。这些发现表明，IL-8在魏尔-帕拉德小体中的储存可能作为EC对先前炎症损伤的“记忆”，从而使细胞能够立即分泌IL-8而无需重新进行蛋白质合成。
