The Cardiovascular Institute, Tokyo, Japan.
Circ J. 2010 Feb;74(2):262-70. doi: 10.1253/circj.cj-09-0644. Epub 2009 Dec 15.
Although clinical studies have suggested a link between inflammation markers and atrial fibrillation (AF), it is still unclear whether local immunologic responses actually exist in human atria during AF.
To address this point, human left appendages were obtained from 16 patients who underwent cardiac surgery (5 with sinus rhythm (SR) and 11 with AF) and subjected to immunohistochemical analysis. In all the AF specimens, adhesion and migration of CD45-reactive cells were consistently observed predominantly in the atrial endo- and subendomyocardium and more prominently than in SR. Most of them were immunologically active CD68-positive macrophages, whereas CD3-positive T cells infiltrated to a lesser extent. Scavenger-receptor A staining revealed maturation of macrophages not in the endocardium but in the midmyocardium, a gradient from endo- to midmyocardium. In the endocardium, along with adhesion molecules (intracellular adhesion molecule-1 and vascular cell adhesion molecule-1), a chemotactic protein-1, which facilitates the recruitment, was more abundantly expressed in AF than in SR. Cytokines including transforming growth factor-beta and interleukin-6 were frequently expressed by these macrophages.
These observations collectively imply active adhesion and recruitment of macrophages across the endocardium in human fibrillating atria, thereby supporting the concept of local immunologic inflammatory responses around the atrial endocardium of AF.
尽管临床研究表明炎症标志物与心房颤动（AF）之间存在关联，但在 AF 期间人类心房中是否确实存在局部免疫反应仍不清楚。
为了解决这一问题，从 16 名接受心脏手术的患者（窦性心律（SR）5 例，AF11 例）中获得了左心耳，并进行了免疫组织化学分析。在所有 AF 标本中，CD45 反应性细胞的黏附和迁移始终主要在心房内膜和心内膜下观察到，并且比 SR 更为明显。它们大多数是免疫活性的 CD68 阳性巨噬细胞，而 CD3 阳性 T 细胞的浸润程度较低。清道夫受体 A 的染色显示，巨噬细胞的成熟不是在心内膜，而是在心中层，从心内膜到心中层存在梯度。在心内膜中，与黏附分子（细胞间黏附分子-1 和血管细胞黏附分子-1）一起，趋化蛋白-1在 AF 中的表达比在 SR 中更为丰富，这有利于募集。这些巨噬细胞经常表达转化生长因子-β和白细胞介素-6 等细胞因子。
这些观察结果共同表明，在人类颤动的心房中，巨噬细胞穿过心内膜积极黏附和募集，从而支持 AF 心房心内膜周围存在局部免疫炎症反应的概念。
