Shi Lei, Tsurusaki Shigeyuki, Futa Noriko, Sakamoto Tamami, Matsuda Tomoko, Nishino Norikazu, Kunitomo Ryuji, Kawasuji Michio, Tokita Kazutaka, Yamamoto Tetsuro
Department of Molecular Pathology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 2-2-1 Honjo, Kumamoto, 860-0811, Japan.
Virchows Arch. 2005 Oct;447(4):747-55. doi: 10.1007/s00428-005-0012-5. Epub 2005 Oct 19.
To elucidate the molecular mechanism inducing monocyte/macrophage infiltration in the atherosclerotic lesion, we measured the monocyte chemotactic capacity in the extracts of aortic lesions. Five out of seven extracts exhibited significant chemotactic activities. Immunohistochemical examination with an anti-CD68 monoclonal antibody demonstrated that the five positive lesions possessed obvious monocyte/macrophage infiltrations at the intima, whereas the two negative lesions did so at significantly lower intensities. We subjected the chemotactic extracts to immunological analyses to identify the monocyte chemoattractant in them. The monocyte chemotactic capacities of all positive extracts were removed with anti-S19 ribosomal protein (RP S19) antibody beads and antimonocyte chemoattractant protein-1 (MCP-1) antibody beads. In three of the five extracts, the anti-RP S19 antibody beads were more effective than the anti-MCP-1 antibody beads for removal, while in the remaining two extracts, the opposite was observed. A combined immunoabsorption with these beads depleted the monocyte chemotactic capacity of a representative sample of each group. Consistently, the chemotactic capacity of an apparently RP S19 dimer-predominant extract was strongly inhibited by the presence of a C5a receptor antagonist. These results suggest that the RP S19 dimer and MCP-1 play a major role in the monocyte/macrophage infiltration of the atherosclerotic vascular lesion.
为阐明动脉粥样硬化病变中诱导单核细胞/巨噬细胞浸润的分子机制，我们检测了主动脉病变提取物中的单核细胞趋化能力。七份提取物中有五份表现出显著的趋化活性。用抗CD68单克隆抗体进行免疫组织化学检查表明，五份阳性病变在内膜处有明显的单核细胞/巨噬细胞浸润，而两份阴性病变的浸润强度明显较低。我们对趋化提取物进行免疫分析，以鉴定其中的单核细胞趋化因子。所有阳性提取物的单核细胞趋化能力均被抗S19核糖体蛋白（RP S19）抗体珠和抗单核细胞趋化蛋白-1（MCP-1）抗体珠去除。在五份提取物中的三份中，抗RP S19抗体珠比抗MCP-1抗体珠去除效果更好，而在其余两份提取物中，观察到相反的情况。用这些珠子进行联合免疫吸附耗尽了每组代表性样本的单核细胞趋化能力。同样，一种明显以RP S19二聚体为主的提取物的趋化能力被C5a受体拮抗剂强烈抑制。这些结果表明，RP S19二聚体和MCP-1在动脉粥样硬化血管病变的单核细胞/巨噬细胞浸润中起主要作用。
