title: The role of ROS in ionizing radiation-induced VLA-4 mediated adhesion of RAW264.7 cells to VCAM-1 under flow conditions.
abstract: Alteration of adhesion molecule expression on endothelial cells has a direct connection with ionizing radiation-induced atherosclerosis, which is an adverse effect observed after radiotherapy. However, minimal attention has been given to monocytes/macrophages role in atherosclerosis development, which are exposed to the radiation at the same time. Under flow conditions using a parallel plate flow chamber to mimic physiological shear stress, we demonstrate here that the avidity between very late antigen-4 (VLA-4) of RAW264.7 cells and its ligand vascular cell adhesion molecule-1 (VCAM-1), was increased after low dose (0.5 Gy) irradiation, but was reduced after higher dose (5 Gy) treatment of ionizing radiation despite the fact that the surface expression of VLA-4 was up-regulated at 5 Gy of ionizing radiation. Treating the cells with free radical scavenger N-acetylcysteine had no effect on VLA-4 expression, but did reduce the avidity between RAW264.7 cells and VCAM-1 to a similar level, independent of ionizing radiation dose. The effect of H(2)O(2) treatment (from 1-100 μM) on RAW264.7 cell adhesion to VCAM-1 generated a similar bell-shaped graph as ionizing radiation. These results suggest that ionizing radiation regulates adhesive interactions between VLA-4 and VCAM-1, and that reactive oxygen species might function as a regulator, for this increased adhesiveness but with altered expression of integrin not play a major role.
authors.affiliation: Edison Biotechnology Institute and Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yuan
authors.forename: Shin Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Shiyong
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D032701:Biomimetics; D002448:Cell Adhesion / Q000528:radiation effects; D002460:Cell Line; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000528:radiation effects; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013312:Stress, Physiological / Q000528:radiation effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D039041:Integrin alpha4beta1; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1