Ikeshita Shunji, Miyatake Yukiko, Otsuka Noriyuki, Kasahara Masanori
Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Exp Mol Pathol. 2014 Aug;97(1):171-5. doi: 10.1016/j.yexmp.2014.07.002. Epub 2014 Jul 2.
Infiltrating macrophages accumulate in fatty streak lesions and transform into foam cells, leading to the formation of atherosclerotic plaques. Inflammatory mechanisms underlying the plaque formation mediated by NKG2D-positive lymphocytes such as CD8+ T cells, natural killer cells and natural killer T cells have been extensively investigated. Yet, the involvement of the NKG2D system itself remains poorly understood. Recent work in mouse models has shown that blockade of an NKG2D receptor-ligand interaction reduces plaque formation and suppresses inflammation in aortae. In this study, we conducted immunohistochemical analysis of NKG2D ligand expression in autopsy-derived aortic specimens. Foam cells expressing NKG2D ligands MICA/B were found in advanced atherosclerotic lesions accompanied by a large necrotic core or hemorrhage. Human monocyte-derived macrophages treated in vitro with acetylated low-density lipoproteins enhanced expression of MICA/B and scavenger receptor A, thus accounting for NKG2D ligand expression in foam cells infiltrating atherosclerotic plaques. Our results suggest that, as in mice, the NKG2D system might be involved in the development of atherosclerosis in humans.
浸润性巨噬细胞在脂纹病变中积聚并转化为泡沫细胞，导致动脉粥样硬化斑块的形成。由NKG2D阳性淋巴细胞（如CD8 + T细胞、自然杀伤细胞和自然杀伤T细胞）介导的斑块形成的炎症机制已得到广泛研究。然而，NKG2D系统本身的参与情况仍知之甚少。最近在小鼠模型中的研究表明，阻断NKG2D受体-配体相互作用可减少斑块形成并抑制主动脉中的炎症。在本研究中，我们对尸检获得的主动脉标本进行了NKG2D配体表达的免疫组织化学分析。在伴有大坏死核心或出血的晚期动脉粥样硬化病变中发现了表达NKG2D配体MICA/B的泡沫细胞。体外经乙酰化低密度脂蛋白处理的人单核细胞衍生巨噬细胞增强了MICA/B和清道夫受体A的表达，从而解释了浸润动脉粥样硬化斑块的泡沫细胞中NKG2D配体的表达。我们的结果表明，与小鼠一样，NKG2D系统可能参与人类动脉粥样硬化的发展。
