Kataoka Noriyuki, Iwaki Kanso, Hashimoto Ken, Mochizuki Seiichi, Ogasawara Yasuo, Sato Masaaki, Tsujioka Katsuhiko, Kajiya Fumihiko
Department of Medical Engineering, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15638-43. doi: 10.1073/pnas.242590799. Epub 2002 Nov 14.
The interaction between monocytes and endothelial cells is considered to play a major role in the early stage of atherosclerosis, and the involved endothelial cell micromechanics may provide us with important aspects of atherogenesis. In the present study, we evaluated (i) the endothelial cell-to-cell and cell-to-substrate gaps with the electric cell-substrate impedance sensing system, which can detect the nanometer order changes of cell-to-cell and cell-to-substrate distances separately, and (ii) the endothelial cell micromechanical properties with an atomic force microscope after application of monocytes to endothelial cells. Application of monocytic THP-1 cells to IL-1beta-stimulated human umbilical vein endothelial cells immediately decreased the electrical resistance of the endothelial cell-to-substrate (increase of the cell-to-substrate gap), whereas the endothelial cell-to-cell resistance (cell-to-cell gap) did not change. The elastic modulus of the endothelial cells decreased after 2-h monocyte application, indicating an increase of endothelial cell deformability. In conclusion, the interaction of the monocytes to the endothelial cells reduced the adhesiveness to the substrate and increased the deformability of endothelial cells. These changes in the adhesiveness and the deformability may facilitate migration of monocytes, a key process of atherogenesis in the later stage.
单核细胞与内皮细胞之间的相互作用被认为在动脉粥样硬化的早期阶段起主要作用，而所涉及的内皮细胞微力学可能为我们提供动脉粥样硬化发生的重要方面。在本研究中，我们使用细胞-基底阻抗传感系统评估了（i）内皮细胞与细胞之间以及细胞与基底之间的间隙，该系统可以分别检测细胞与细胞之间以及细胞与基底之间距离的纳米级变化，并且（ii）在将单核细胞应用于内皮细胞后，使用原子力显微镜评估了内皮细胞的微力学特性。将单核细胞THP-1细胞应用于白细胞介素-1β刺激的人脐静脉内皮细胞后，立即降低了内皮细胞与基底之间的电阻（细胞与基底间隙增加），而内皮细胞与细胞之间的电阻（细胞与细胞间隙）没有变化。单核细胞应用2小时后，内皮细胞的弹性模量降低，表明内皮细胞的可变形性增加。总之，单核细胞与内皮细胞的相互作用降低了与基底的粘附性，并增加了内皮细胞的可变形性。粘附性和可变形性的这些变化可能促进单核细胞的迁移，这是后期动脉粥样硬化发生的关键过程。
