Methe Heiko, Hess Shmuel, Edelman Elazer R
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Thromb Haemost. 2007 Aug;98(2):278-82.
The endothelium is a highly specialized active interface between blood and the underlying tissues, maintaining vascular tone, thrombo-resistance and selective permeability to cells and proteins. It is also an important regulator of inflammatory diseases, and endothelial-leukocyte interactions often herald complex diseases with an inflammatory component. Yet, the exact mechanisms promoting immune activation of endothelial cells (EC) are incompletely understood. Knowledge is accumulating that the immediate environment defines the cellular phenotype, whereby matrix composition and spatial formation (three- versus two-dimensional) seem to act as pivotal mediators. Here we summarize current findings denoting a key role of matrix environment in regulating endothelial immunogenicity. The immune response to three-dimensional matrix-embedded EC stands in stark contrast to the response engendered by injection of these same cells in their free state. Matrix-embedding confers a quiescent endothelial state with reduced expression levels of chemokines, adhesion, costimulatory, and major histocompatibility complex II molecules. Compared to EC grown on two-dimensional tissue culture plates, cytokine-stimulation of matrix-embedded EC results in significantly reduced adhesion of natural killer cells and proliferation of co-cultivated allogeneic T cells. On the contrary, matrix-embedded EC induce an immune-inhibitory phenotype of dendritic cells and T regulatory cells to a greater extent than non-embedded EC. As vascular diseases are associated with profound changes in basement membrane composition and overall tissue architecture, our results indicate that the immediate environment of EC might play a pivotal role in initiating and regulating of different vascular diseases. Cell-matrix interconnections appear to govern endothelial immunogenicity and interactions between EC and immune cells.
内皮是血液与下方组织之间高度特化的活性界面，维持血管张力、抗血栓形成能力以及对细胞和蛋白质的选择性通透性。它也是炎症性疾病的重要调节因子，内皮细胞与白细胞的相互作用往往预示着伴有炎症成分的复杂疾病。然而，促进内皮细胞（EC）免疫激活的确切机制尚未完全明了。越来越多的知识表明，直接环境决定细胞表型，其中基质组成和空间形态（三维与二维）似乎起着关键介导作用。在此，我们总结当前的研究发现，这些发现表明基质环境在调节内皮免疫原性方面发挥着关键作用。对三维基质包埋的内皮细胞的免疫反应与注射相同游离状态细胞所引发的反应形成鲜明对比。基质包埋赋予内皮细胞静止状态，趋化因子、黏附分子、共刺激分子和主要组织相容性复合体II类分子的表达水平降低。与在二维组织培养板上生长的内皮细胞相比，细胞因子刺激基质包埋的内皮细胞会导致自然杀伤细胞的黏附显著减少以及共培养的同种异体T细胞增殖减少。相反，基质包埋的内皮细胞比未包埋的内皮细胞在更大程度上诱导树突状细胞和调节性T细胞产生免疫抑制表型。由于血管疾病与基底膜组成和整体组织结构的深刻变化相关，我们的结果表明内皮细胞的直接环境可能在不同血管疾病的启动和调节中起关键作用。细胞与基质的相互连接似乎决定着内皮免疫原性以及内皮细胞与免疫细胞之间的相互作用。
