A revised model for the secretion of tPA and cytokines from cultured endothelial cells
A revised model for the secretion of tPA and cytokines from cultured endothelial cells
复制标题
DOI：
10.1182/blood-2010-03-276170
复制
发表时间：
2010-09-23
期刊：
影响因子：
20.3
通讯作者：
Carter, Tom
中科院分区：
文献类型：
--
作者：
Knipe, Laura;Meli, Athinoula;Carter, Tom
据报道，内皮细胞含有几种不同的受调节的分泌细胞器，包括韦贝尔-帕拉德小体（WPBs）、组织纤溶酶原激活物（tPA）细胞器和含2型趋化因子的细胞器。我们发现，人内皮细胞中的tPA和2型细胞器代表一个单独的室，主要负责不受刺激的tPA分泌，或者在暴露于白细胞介素-1 β (IL-1 β)的细胞中，细胞因子IL-8、IL-6、单核细胞趋化蛋白-1 （MCP-1）和生长调节癌基因α (gro - α)。与WPBs不同的是，它缺乏可检测到的血管性血友病因子、p选择素、Rab27a或CD63免疫反应性，颗粒内pH值无时间依赖性下降，可检测到未受刺激的胞外分泌，对Ca2+升高分泌物的反应非常差。WPBs还可能含有tPA，在IL-1 β处理的细胞中，含有IL-8、IL-6、MCP-1和gro - α，是组胺或离子霉素刺激下这些分子分泌的主要来源。然而，细胞因子和tPA的储存效率分析显示，与血管性血友病因子相比，它们的储存效率都很低。非哺乳动物的非分泌蛋白EGFP在分泌途径中表达时，也进入WPBs，并具有与tPA和所测试的细胞因子相似的储存效率。基于这些数据，我们提出了一个修正的细胞因子和tPA的储存和分泌模型。(血。2010;116 (12):2183 - 2191)
Endothelial cells are reported to contain several distinct populations of regulated secretory organelles, including Weibel-Palade bodies (WPBs), the tissue plasminogen activator (tPA) organelle, and the type-2 chemokine-containing organelle. We show that the tPA and type-2 organelles in human endothelial cells represent a single compartment primarily responsible for unstimulated secretion of tPA or, in cells exposed to interleukin-1 beta (IL-1 beta), the cytokines IL-8, IL-6, monocyte chemoattractant protein-1 (MCP-1), and growth-regulated oncogene-alpha (GRO-alpha). This compartment was distinct from WPBs in that it lacked detectable von Willebrand factor, P-selectin, Rab27a, or CD63 immunoreactivity, displayed no time-dependent decrease in intragranule pH, underwent detectable unstimulated exocytosis, and was very poorly responsive to Ca2+ -elevating secretagogues. WPBs could also contain tPA, and in IL-1 beta-treated cells, IL-8, IL-6, MCP-1, and GRO-alpha, and were the primary source for histamine or ionomycin-stimulated secretion of these molecules. However, analysis of the storage efficiency of cytokines and tPA revealed that all were very poorly stored compared with von Willebrand factor. The nonmammalian, nonsecretory protein EGFP, when expressed in the secretory pathway, also entered WPBs and had a storage efficiency similar to tPA and the cytokines tested. Based on these data, we proposed a revised model for storage and secretion of cytokines and tPA. (Blood. 2010;116(12):2183-2191)