Institute of Physiology II, University of Münster, Germany.
Anal Bioanal Chem. 2011 Mar;399(7):2351-8. doi: 10.1007/s00216-010-3978-z. Epub 2010 Jul 16.
A demanding task of medicine is to understand and control the immune system. Central players in the cellular immune response are the leukocytes that leave the blood stream for host defense. Endothelial cells limit the emigration rate of leukocytes. Being located between blood and tissues, they permit or deny the passage. The exact mechanism of this process called diapedesis is not solved yet. Leukocytes can principally traverse either between cells (paracellularly) or directly through an individual endothelial cell (transcellularly). The transcellular way has recently gained experimental support, but it is not clear how the endothelial cytoskeleton manages to open and close a transmigratory channel. Atomic force microscopy was used to investigate the endothelial cytoskeleton. In order to directly access the leukocyte-endothelial interaction site, we applied a special protocol ("nanosurgery"). As a result, the endothelial cell turned out to become softer in a confined region strictly underneath the leukocyte. Fluorescence microscopy confirmed a depolymerization of the f-actin strands at the invasion site. Leukocytes dramatically rearrange the endothelial cytoskeleton to form transmigratory channels.
医学的一项艰巨任务是理解和控制免疫系统。细胞免疫反应的核心参与者是白细胞,它们离开血液流进行宿主防御。内皮细胞限制白细胞的迁移率。作为血液和组织之间的连接,它们允许或拒绝通过。这个过程被称为穿胞作用,其确切机制尚未解决。白细胞主要可以通过细胞之间(细胞旁途径)或直接穿过单个内皮细胞(细胞内途径)进行迁移。最近,细胞内途径得到了实验支持,但内皮细胞骨架如何打开和关闭穿胞通道尚不清楚。原子力显微镜被用于研究内皮细胞骨架。为了直接访问白细胞-内皮细胞相互作用部位,我们应用了一种特殊的方案(“纳米手术”)。结果表明,在白细胞正下方的一个受限区域内,内皮细胞变得更加柔软。荧光显微镜证实,入侵部位的 F-actin 链发生解聚。白细胞会剧烈地重新排列内皮细胞骨架以形成穿胞通道。