Møller F, Andersen C B, Nielsen L B
Department of Clinical Biochemistry, University of Copenhagen, Denmark.
Scand J Clin Lab Invest. 2005;65(7):559-70. doi: 10.1080/00365510500321564.
Although T and B lymphocytes accumulate in atherosclerotic lesions and play a key role in their growth, the mechanisms involved in the adhesion and recruitment of T and B lymphocytes by the lesions have not been resolved. The aim of this study was to compare T and B lymphocyte adhesion to atherosclerotic arteries and to test the role of VCAM-1 and ICAM-1.
T and B lymphocytes were labelled with red and green fluorescent dyes and incubated with freshly isolated aortas from apolipoprotein-E-deficient mice. In some experiments the aortas were pre-incubated with specific monoclonal antibodies. After washing, the adhering cells were detected by confocal laser scanning microscopy.
The number of T and B lymphocytes that adhered to the aortic intimal surface was similar in both lesioned and non-lesioned areas and in the shoulder region of the lesions. However, the adhesion of T and B lymphocytes was significantly higher in the shoulder regions compared with the lesioned (p<0.0001) and non-lesioned areas of the aorta (p<0.0001). After pre-incubation of the aortas with antibodies against VCAM-1 or ICAM-1, the lymphocyte adhesions in lesioned areas were 42 % (p = 0.04) and 55 % (p = 0.17), respectively, of those in lesioned areas that had been pre-incubated with a control antibody. However, although VCAM-1 protein expression was most pronounced in the shoulder region, the lymphocyte adhesions in the shoulder region and in non-lesioned areas were unaffected by pre-incubation with VCAM-1 antibodies.
The results suggest that adhesion of T and B lymphocytes to mouse aortic endothelium is similar, is affected by lesion topology and is dependent on VCAM-1 expression over the core of atherosclerotic lesions.
尽管T淋巴细胞和B淋巴细胞在动脉粥样硬化病变中积聚并在其发展过程中起关键作用,但病变部位对T淋巴细胞和B淋巴细胞的黏附及募集机制尚未明确。本研究旨在比较T淋巴细胞和B淋巴细胞与动脉粥样硬化动脉的黏附情况,并检测血管细胞黏附分子-1(VCAM-1)和细胞间黏附分子-1(ICAM-1)的作用。
用红色和绿色荧光染料标记T淋巴细胞和B淋巴细胞,并与从载脂蛋白E缺陷小鼠新鲜分离的主动脉共同孵育。在一些实验中,主动脉预先与特异性单克隆抗体孵育。洗涤后,通过共聚焦激光扫描显微镜检测黏附细胞。
在病变区域和非病变区域以及病变的肩部区域,黏附于主动脉内膜表面的T淋巴细胞和B淋巴细胞数量相似。然而,与主动脉的病变区域(p<0.0001)和非病变区域(p<0.0001)相比,T淋巴细胞和B淋巴细胞在肩部区域的黏附明显更高。用抗VCAM-1或抗ICAM-1抗体预先孵育主动脉后,病变区域的淋巴细胞黏附分别为用对照抗体预先孵育的病变区域的42%(p = 0.04)和55%(p = 0.17)。然而,尽管VCAM-1蛋白表达在肩部区域最为明显,但肩部区域和非病变区域的淋巴细胞黏附不受VCAM-1抗体预先孵育的影响。
结果表明,T淋巴细胞和B淋巴细胞与小鼠主动脉内皮的黏附相似,受病变拓扑结构影响,且依赖于动脉粥样硬化病变核心区域的VCAM-1表达。