Translational Medicine Laboratory, Department of Internal and Agricultural Medicine, Jagiellonian University School of Medicine, J Dietl Hospital, Ul Skarbowa 1, 31-121 Cracow, Poland.
Thromb Haemost. 2012 Nov;108(5):812-23. doi: 10.1160/TH12-05-0339. Epub 2012 Sep 5.
Intraluminal thrombus formation in aortic abdominal aneurysms (AAA) is associated with adverse clinical prognosis. Interplay between coagulation and inflammation, characterised by leukocyte infiltration and cytokine production, has been implicated in AAA thrombus formation. We studied leukocyte (CD45+) content by flow cytometry in AAA thrombi from 27 patients undergoing surgical repair. Luminal parts of thrombi were leukocyte-rich, while abluminal segments showed low leukocyte content. CD66b+ granulocytes were the most prevalent, but their content was similar to blood. Monocytes (CD14+) and T cells (CD3+) were also abundant, while content of B lymphocytes (CD19+) and NK cells (CD56+CD16+) were low. Thrombi showed comparable content of CD14highCD16- monocytes and lower CD14highCD16+ and CD14dimCD16+, than blood. Monocytes were activated with high CD11b, CD11c and HLA-DR expression. Total T cell content was decreased in AAA thrombus compared to peripheral blood but CD8 and CD3+CD4-CD8- (double negative T cell) contents were increased in thrombi. CD4+ cells were lower but highly activated (high CD69, CD25 and HLA-DR). No differences in T regulatory (CD4+CD25+FoxP3+) cell or pro-atherogenic CD4+CD28null lymphocyte content were observed between thrombi and blood. Thrombus T cells expressed high levels of CCR5 receptor for chemokine RANTES, commonly released from activated platelets. Leukocyte or T cell content in thrombi was not correlated with aneurysm size. However, CD3+ content was significantly associated with smoking in multivariate analysis taking into account major risk factors for atherosclerosis. In conclusion, intraluminal AAA thrombi are highly inflamed, predominantly with granulocytes, CD14highCD16- monocytes and activated T lymphocytes. Smoking is associated with T cell infiltration in AAA intraluminal thrombi.
腹主动脉瘤(AAA)中的腔内血栓形成与不良的临床预后相关。凝血和炎症之间的相互作用,其特征在于白细胞浸润和细胞因子产生,与 AAA 血栓形成有关。我们通过流式细胞术研究了 27 例接受手术修复的患者的 AAA 血栓中的白细胞(CD45+)含量。血栓的管腔部分富含白细胞,而外膜部分白细胞含量较低。CD66b+粒细胞最为常见,但含量与血液相似。单核细胞(CD14+)和 T 细胞(CD3+)也很丰富,而 B 淋巴细胞(CD19+)和 NK 细胞(CD56+CD16+)含量较低。与血液相比,血栓中的 CD14highCD16-单核细胞含量相当,但 CD14highCD16+和 CD14dimCD16+含量较低。单核细胞的激活程度较高,表达高水平的 CD11b、CD11c 和 HLA-DR。与外周血相比,AAA 血栓中的总 T 细胞含量减少,但 CD8 和 CD3+CD4-CD8-(双阴性 T 细胞)含量增加。CD4+细胞含量较低,但高度激活(高 CD69、CD25 和 HLA-DR)。在血栓和血液之间未观察到 T 调节(CD4+CD25+FoxP3+)细胞或促动脉粥样硬化性 CD4+CD28null 淋巴细胞含量的差异。血栓中的 T 细胞表达趋化因子 RANTES 的 CCR5 受体,RANTES 通常从激活的血小板中释放。在考虑动脉粥样硬化主要危险因素的多变量分析中,血栓中的白细胞或 T 细胞含量与动脉瘤大小无关。然而,CD3+含量与吸烟显著相关。总之,AAA 腔内血栓高度炎症,主要是粒细胞、CD14highCD16-单核细胞和活化的 T 淋巴细胞。吸烟与 AAA 腔内血栓中的 T 细胞浸润有关。