Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
Biochem Biophys Res Commun. 2010 Jun 25;397(2):251-6. doi: 10.1016/j.bbrc.2010.05.094. Epub 2010 Jun 1.
While intercellular adhesion molecule-1 (ICAM-1) is a transmembrane protein, two types of extracellular ICAM-1 have been detected in cell culture supernatants as well as in the serum: a soluble form of ICAM-1 (sICAM-1) and a membranous form of ICAM-1 (mICAM-1) associated with exosomes. Previous observations have demonstrated that sICAM-1 cannot exert potent immune modulatory activity due to its low affinity for leukocyte function-associated antigen-1 (LFA-1) or membrane attack complex-1. In this report, we initially observed that human cancer cells shed mICAM-1(+)-exosomes but were devoid of vascular cell adhesion molecule-1 and E-selectin. We demonstrate that mICAM-1 on exosomes retained its topology similar to that of cell surface ICAM-1, and could bind to leukocytes. In addition, we show that exosomal mICAM-1 exhibits potent anti-leukocyte adhesion activity to tumor necrosis factor-alpha-activated endothelial cells compared to that of sICAM-1. Taken together with previous findings, our results indicate that mICAM-1 on exosomes exhibits potent immune modulatory activity.
细胞间黏附分子-1（ICAM-1）是一种跨膜蛋白，但在细胞培养上清液和血清中还检测到两种类型的细胞外 ICAM-1：可溶性 ICAM-1（sICAM-1）和与外泌体相关的膜结合 ICAM-1（mICAM-1）。先前的观察结果表明，由于 sICAM-1 与白细胞功能相关抗原-1（LFA-1）或膜攻击复合物-1的亲和力低，因此不能发挥有效的免疫调节活性。在本报告中，我们最初观察到人类癌细胞脱落 mICAM-1(+)-外泌体，但缺乏血管细胞黏附分子-1 和 E-选择素。我们证明外泌体上的 mICAM-1 保留了与其在细胞表面上的拓扑结构相似的结构，并且可以与白细胞结合。此外，我们还表明，与 sICAM-1 相比，外泌体 mICAM-1 对肿瘤坏死因子-α激活的内皮细胞具有更强的抗白细胞黏附活性。结合以前的发现，我们的结果表明外泌体上的 mICAM-1 具有强大的免疫调节活性。
