Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells
Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells
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DOI：
10.1161/01.cir.98.1.1
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发表时间：
1998-07-07
期刊：
影响因子：
37.8
通讯作者：
Wagner, WR
中科院分区：
文献类型：
--
作者：
Villanueva, FS;Jankowski, RJ;Wagner, WR
临床前动脉粥样硬化与内皮细胞白细胞粘附分子表达增加有关，白细胞粘附分子在动脉粥样硬化形成过程中介导单核细胞粘附。细胞表面LAMs的鉴定可以唯一地允许评估内皮功能，但是没有用于检测LAMs的体内方法。我们测试了一种新的微泡，设计结合，并允许特定的细胞间粘附分子-1（ICAM-1）的超声检测方法和结果-全氟丁烷充气脂质衍生微球与ICAM-1的单克隆抗体共价结合的气泡壳合成。合成在壳上具有非特异性IgG或没有蛋白质的气泡作为对照。将培养的人冠状动脉EC的盖玻片置于平行板灌注室中，并暴露于3种微泡中的一种，然后用培养基灌注。用正常或白细胞介素-1 β激活的内皮细胞过度表达ICAM-1进行实验，并用荧光显微镜定量气泡粘附。对照气泡对正常或活化的EC的粘附有限，而与正常EC相比，当抗ICAM-1结合的气泡暴露于活化的EC时，粘附增加40倍（每个细胞分别为8.1+/-3.5和0.21+/-0.09个气泡，P
Background-Preclinical atherosclerosis is associated with increased endothelial cell (EC) expression of leukocyte adhesion molecules (LAMs), which mediate monocyte adhesion during atherogenesis. Identification of cell-surface LAMs may uniquely allow assessment of endothelial function, but there are no in vivo methods for detecting LAMs,. We tested a new microbubble designed to bind to and allow specific ultrasound detection of intercellular adhesion molecule-1 (ICAM-1).Methods and Results-A perfluorobutane gas-filled lipid-derived microsphere with monoclonal antibody to ICAM-1 covalently bound to the bubble shell was synthesized. Bubbles with either nonspecific IgG or no protein on the shell were synthesized as controls. Coverslips of cultured human coronary artery ECs were placed in a parallel-plate perfusion chamber and exposed to 1 of the 3 microbubble species, followed by perfusion with culture medium. Experiments were performed with either normal or interleukin-1 beta-activated ECs overexpressing ICAM-1, and bubble adherence was quantified with epifluorescent videomicroscopy. There was limited adherence of control bubbles to normal or activated ECs, whereas a 40-fold increase in adhesion occurred when anti-ICAM-1-conjugated bubbles were exposed to activated ECs compared with normal ECs (8.1+/-3.5 versus 0.21+/-0.09 bubbles per cell, respectively, P