Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Radiat Res. 2012 May;177(5):594-601. doi: 10.1667/rr2557.1. Epub 2011 Nov 15.
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.
暴露于各种来源的辐射会增加患心脏病和中风的风险。由于辐射也会引发炎症，一种可能的机制是血管内皮细胞黏附性的改变，从而触发白细胞的促动脉粥样硬化积聚。为了在细胞水平上研究这种机制，测定了 X 射线对培养的人主动脉内皮细胞（HAEC）黏附性的影响。HAEC 单层生长，并在生理切变应力下用流动室黏附测定法测定 0 至 30 Gy X 射线照射后的黏附性。照射后 24 小时，HAEC 的黏附性增加，在 15 Gy 时达到峰值效应。辐射对内皮细胞黏附分子 ICAM-1 和 VCAM-1 的表面表达没有显著影响。然而，白细胞整合素受体对 ICAM-1 和 VCAM-1 的抗体阻断消除了辐射诱导的黏附性。由于这些白细胞整合素可以被内皮细胞表面呈现的趋化因子激活，因此测试了百日咳毒素（PTX）的作用，PTX 是一种趋化因子介导的整合素激活抑制剂。PTX 特异性抑制辐射诱导的黏附性，对未照射的细胞没有显著影响。因此，即使涉及的黏附分子表达增加，辐射也通过内皮细胞向白细胞的趋化因子依赖性信号诱导主动脉内皮细胞的黏附性增加。
