Weyand Cornelia M, Goronzy Jörg J
Department of Medicine, Mayo Medical and Graduate Schools, Rochester, MN, USA.
Cleve Clin J Med. 2002;69 Suppl 2:SII28-32. doi: 10.3949/ccjm.69.suppl_2.sii28.
T lymphocytes, encountering stimulatory signals in the adventitia of medium-size arteries, emerge as the key players in inflammation-associated injury pathways. In GCA, all injury mechanisms have been related to effector macrophages. Regulated by IFN-gamma-producing T cells, macrophages commit to distinct avenues of differentiation and acquire a spectrum of potentially harmful capabilities (Figure 1). Macrophages in the adventitia focus on production of pro-inflammatory cytokines. Macrophages in the media specialize in oxidative damage with lipid peroxidation attacking smooth muscle cells and matrix components. These macrophages also supply reactive oxygen intermediates that, in combination with nitrogen intermediates, cause protein nitration of endothelial cells. Production of oxygen radicals is complemented by the production of metalloproteinases, likely essential in the breakdown of elastic membranes. With the fragmentation of the internal elastic lamina, the intimal layer becomes accessible to migratory myofibroblasts that, driven by PDGF, form a hyperplastic intimal layer and cause occlusion of the vessel lumen. Expansion of the hyperplastic intima is accompanied by intense neoangiogenesis, supported by angiogenesis factors that again derive from specialized macrophages. Similarities in injury pathways between GCA and another arterial disease, atherosclerosis, are beginning to be recognized. Specifically, activated T cells and macrophages are increasingly appreciated as key players in the process of instability and rupture of atherosclerotic plaque. A specialized subset of CD4 T cells, CD4+ CD28- T cells, are suspected to participate in tissue injury in the plaque. These T cells are equipped with cytolytic capabilities and release large amounts of IFN-gamma. Comparative studies between patients with GCA and those with acute coronary syndromes should enhance our ability to define the principles of arterial wall inflammation, the specifics of injury in that microenvironment, and help in the identification of the eliciting signals.
T淋巴细胞在中等大小动脉外膜中遇到刺激信号后，成为炎症相关损伤途径的关键参与者。在巨细胞动脉炎（GCA）中，所有损伤机制都与效应巨噬细胞有关。在产生γ干扰素的T细胞调节下，巨噬细胞走上不同的分化途径，并获得一系列潜在的有害能力（图1）。外膜中的巨噬细胞专注于促炎细胞因子的产生。中膜中的巨噬细胞则专门进行氧化损伤，脂质过氧化攻击平滑肌细胞和基质成分。这些巨噬细胞还提供活性氧中间体，与氮中间体结合，导致内皮细胞的蛋白质硝化。氧自由基的产生伴随着金属蛋白酶的产生，这可能对弹性膜的分解至关重要。随着内弹性膜的断裂，内膜层变得可被迁移的肌成纤维细胞接触，这些细胞在血小板衍生生长因子（PDGF）的驱动下，形成增生性内膜层并导致血管腔阻塞。增生性内膜的扩张伴随着强烈的新生血管形成，这由同样源自特殊巨噬细胞的血管生成因子所支持。GCA与另一种动脉疾病动脉粥样硬化之间损伤途径的相似性正开始被认识到。具体而言，活化的T细胞和巨噬细胞越来越被视为动脉粥样硬化斑块不稳定和破裂过程中的关键参与者。CD4 T细胞的一个特殊亚群，CD4 + CD28 - T细胞，被怀疑参与斑块中的组织损伤。这些T细胞具备细胞溶解能力并释放大量的γ干扰素。对GCA患者和急性冠状动脉综合征患者的比较研究应能增强我们定义动脉壁炎症原理、该微环境中损伤细节的能力，并有助于识别引发信号。
