A membranous form of ICAM-1 on exosomes efficiently blocks leukocyte adhesion to activated endothelial cells

• DOI: 10.1016/j.bbrc.2010.05.094
• Publication Date: 2010-06-02T05:34:21Z
• Authors: Hwan Myung Lee; Eun-Jeong Choi; Ji Hyun Kim; Thomas Doohun Kim; Yoon-Keun Kim; Chulhun Kang; Yong Song Gho
• Keywords: 0301 basic medicine; DIMERIZATION; SICAM-1; ICAM-1; Communicasome; Vascular Cell Adhesion Molecule-1; DISTINCT; Microparticles; Exosomes; MOLECULE-1; VESICLES; Cell Line; 03 medical and health sciences; Endothelial cell; Cell Adhesion; Leukocytes; Humans; CANCER CELLS; GENE-EXPRESSION; MICROVESICLES; Inflammation; Endothelial Cells; Intercellular Adhesion Molecule-1; 3. Good health; E-Selectin

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.