title: Ionizing radiation increases adhesiveness of human aortic endothelial cells via a chemokine-dependent mechanism.
abstract: Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. Since radiation also induces inflammation, a possible mechanism is a change in the adhesiveness of vascular endothelial cells, triggering pro-atherogenic accumulation of leukocytes. To investigate this mechanism at the cellular level, the effect of X rays on adhesiveness of cultured human aortic endothelial cells (HAECs) was determined. HAECs were grown as monolayers and exposed to 0 to 30 Gy X rays, followed by measurement of adhesiveness under physiological shear stress using a flow chamber adhesion assay. Twenty-four hours after irradiation, HAEC adhesiveness was increased, with a peak effect at 15 Gy. Radiation had no significant effect on surface expression of the endothelial adhesion molecules ICAM-1 and VCAM-1. Antibody blockade of the leukocyte integrin receptors for ICAM-1 and VCAM-1, however, abolished the radiation-induced adhesiveness. Since these leukocyte integrins can be activated by chemokines presented on the endothelial cell surface, the effect of pertussis toxin (PTX), an inhibitor of chemokine-mediated integrin activation, was tested. PTX specifically inhibited radiation-induced adhesiveness, with no significant effect on nonirradiated cells. Therefore, radiation induces increased adhesiveness of aortic endothelial cells through chemokine-dependent signaling from endothelial cells to leukocytes, even in the absence of increased expression of the adhesion molecules involved.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Saman
authors.initials: S
authors.lastname: Khaled
authors.forename: Kiran B
authors.initials: KB
authors.lastname: Gupta
authors.forename: Dennis F
authors.initials: DF
authors.lastname: Kucik
mesh_terms: D001011:Aorta / Q000166:cytology*; D017209:Apoptosis / Q000528:radiation effects; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects*; D002478:Cells, Cultured / Q000502:physiology / Q000528:radiation effects; D054377:Chemokine CXCL12 / Q000494:pharmacology; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D036904:Leukocyte Rolling / Q000187:drug effects; D018715:Microscopy, Video; D009000:Monocytes / Q000502:physiology; D037342:Pertussis Toxin / Q000494:pharmacology; D012212:Rheology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D014657:Vasculitis / Q000209:etiology / Q000473:pathology
chemical_list: D018821:CD18 Antigens; D054377:Chemokine CXCL12; D018925:Chemokines; D019012:Integrin beta1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D037342:Pertussis Toxin