Bobryshev Y V, Lord R S
Surgical Professorial Unit, St. Vincent's Hospital, University of New South Wales, Sydney, Australia.
Cardiovasc Res. 1998 Mar;37(3):799-810. doi: 10.1016/s0008-6363(97)00229-0.
We previously demonstrated that vascular dendritic cells (VDCs) are present in the intima of large arteries and that their numbers are increased in atherosclerotic lesions. This study was undertaken to determine whether VDCs are involved in immune-mediated reactions in atherogenesis.
Specimens of carotid artery and aorta were obtained at operation. VDCs were identified with anti-CD1a or with S-100. Co-localisation of VDCs with different intimal cells, including T-cells and macrophages, was studied using a double immunostaining procedure. In areas where the co-localising cells were detected, the peculiarities of expression of HLA-DR, ICAM-1, VCAM-1 were examined.
In all the atherosclerotic plaques, VDCs were seen in contact with T-cells, but these co-localising cells were irregularly distributed and were mainly found in zones of neovascularisation containing inflammatory infiltrates. In other areas, T-cell/VDC co-localisation was rarely detected but VDCs were often found in contact with macrophages. VDCs were detected also in the media beneath atherosclerotic lesions and in the adventitia, where they were mostly around vasa vasorum, especially in areas exhibiting signs of acute inflammation. In these areas VDCs expressed ICAM-1, VCAM-1 and were in contact with T-cells. In both plaques and in the adventitia, the areas with co-localising VDCs and T-cells corresponded to the areas with HLA-DR expression.
The results suggest that VDCs are involved in T-cell activation in atherogenesis. There are two regions within the arterial wall where VDC/T-cell co-localisation mostly occurs, namely, in zones of neovascularisation containing inflammatory infiltrates located within atherosclerotic lesions, and in areas with inflammatory infiltrates around vasa vasorum in the adventitia. Possibly, some intimal VDCs migrate through the media and adventitia to adjacent lymph nodes where they present atherosclerosis associated antigens. We also speculate that VDC/macrophage contacts are essential in processing immune information in atherogenesis.
我们之前证实,血管树突状细胞(VDCs)存在于大动脉内膜,且其数量在动脉粥样硬化病变中增加。本研究旨在确定VDCs是否参与动脉粥样硬化形成过程中的免疫介导反应。
手术时获取颈动脉和主动脉标本。用抗CD1a或S-100鉴定VDCs。采用双重免疫染色法研究VDCs与不同内膜细胞(包括T细胞和巨噬细胞)的共定位。在检测到共定位细胞的区域,检查HLA-DR、ICAM-1、VCAM-1的表达特点。
在所有动脉粥样硬化斑块中,可见VDCs与T细胞接触,但这些共定位细胞分布不规则,主要见于含有炎性浸润的新生血管区域。在其他区域,很少检测到T细胞/VDC共定位,但VDCs常与巨噬细胞接触。在动脉粥样硬化病变下方的中膜和外膜也检测到VDCs;在这些部位,VDCs主要围绕在血管滋养血管周围,尤其是在有急性炎症迹象的区域。在这些区域,VDCs表达ICAM-1、VCAM-1,并与T细胞接触。在斑块和外膜中,VDCs与T细胞共定位的区域与HLA-DR表达区域相对应。
结果表明,VDCs参与动脉粥样硬化形成过程中的T细胞活化。动脉壁内主要有两个区域发生VDC/T细胞共定位,即动脉粥样硬化病变内含有炎性浸润的新生血管区域,以及外膜中血管滋养血管周围有炎性浸润的区域。可能一些内膜VDCs通过中膜和外膜迁移至相邻淋巴结,在那里呈递动脉粥样硬化相关抗原。我们还推测,VDC/巨噬细胞接触在动脉粥样硬化形成过程中的免疫信息处理中至关重要。