Abstract 4343: Ionizing radiation reduces VLA4 mediated adhesion of macrophage via generation of ROS

Abstract

Abstract Adhesion molecules have direct connection with radiation-associated atherosclerosis which is an adverse effect observed after radiation therapy, but the mechanism is still not fully understood. Considerable interest has been focused on the effect of radiation on endothelial cells. Previous work has demonstrated that adhesion molecules of endothelium are up-regulated after exposure to ionizing radiation, which facilitates adhesion of leukocytes and lymphocytes. However, as the initiator in the atherosclerosis development, not enough attention was paid to macrophages which are exposed to the same radiation. In this study, we report that the adhesion between very late Antigen-4 (VLA-4) and its ligand vascular cell adhesion molecule-1 (VCAM-1), the most important adhesion molecules for atherosclerotic lesion formation, was reduced after a clinical dose of radiation (5 Gy). All the adhesion evaluations were tested under flow conditions by using a parallel plate flow chamber to mimick physiological shear stress. We found that the adhesion decreased after irradiation despite macrophage surface expression of VLA-4 was up-regulated in a time dependent manner. Total level of alpha-4 integrin increased whereas beta-1 had no change. Pretreatment with free radical scavenger N-acetylcysteine (NAC) did not change integrin expression but eliminated the adhesion difference following irradiation. Taken together, we hypothesize high levels of ROS generated by ionizing radiation inhibits the affinity of VLA-4 to VCAM-1, in which integrin expression is not the dominant factor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4343. doi:1538-7445.AM2012-4343