Galkina Elena, Kadl Alexandra, Sanders John, Varughese Danielle, Sarembock Ian J, Ley Klaus
Department of Biomedical Engineering, University of Virginia, Health Sciences Center, Charlottesville, VA 22908, USA.
J Exp Med. 2006 May 15;203(5):1273-82. doi: 10.1084/jem.20052205. Epub 2006 May 8.
Atherosclerosis is an inflammatory disease of large arteries. Flow cytometry of aortic cell suspensions showed that B and T lymphocytes and some macrophages and dendritic cells are already present in the adventitia of normal/noninflamed mouse aortas. Adoptively transferred lymphocytes constitutively homed to the aorta and resided within the adventitia up to 7 d after transfer. Lymphocyte trafficking into normal/noninflamed or atherosclerosis-prone aortas was partially L-selectin dependent. Antigen-activated dendritic cells induced increased T lymphocyte proliferation within the aorta 72 h after adoptive transfer. During progression of atherosclerosis in apolipoprotein-E-deficient mice, the total number of macrophages, T cells, and dendritic cells, but not B cells, increased significantly. This alteration in immune cell composition was accompanied by the formation of tertiary lymphoid tissue in the adventitia of atherosclerotic aortas. These results demonstrate that lymphocytes already reside within the normal/noninflamed aorta before the onset atherosclerosis as a consequence of constitutive trafficking. Atherosclerosis induces the recruitment of macrophages and dendritic cells that support antigen presentation.
动脉粥样硬化是一种累及大动脉的炎症性疾病。对主动脉细胞悬液进行流式细胞术分析显示,在正常/未发炎的小鼠主动脉外膜中已存在B淋巴细胞、T淋巴细胞以及一些巨噬细胞和树突状细胞。过继转移的淋巴细胞持续归巢至主动脉,并在转移后7天内一直驻留在外膜中。淋巴细胞向正常/未发炎或易患动脉粥样硬化的主动脉的迁移部分依赖于L-选择素。抗原激活的树突状细胞在过继转移72小时后可诱导主动脉内T淋巴细胞增殖增加。在载脂蛋白E缺陷小鼠的动脉粥样硬化进展过程中,巨噬细胞、T细胞和树突状细胞(而非B细胞)的总数显著增加。免疫细胞组成的这种改变伴随着动脉粥样硬化主动脉外膜中三级淋巴组织的形成。这些结果表明,由于持续的迁移,淋巴细胞在动脉粥样硬化发病前就已存在于正常/未发炎的主动脉内。动脉粥样硬化会诱导支持抗原呈递的巨噬细胞和树突状细胞的募集。