Kanamoto Ryo, Aoki Hiroki, Furusho Aya, Otsuka Hiroyuki, Shintani Yusuke, Tobinaga Satoru, Hiromatsu Shinichi, Fukumoto Yoshihiro, Tanaka Hiroyuki
Division of Cardiovascular Surgery, Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Cardiovascular Research Institute, Kurume University, Kurume, Fukuoka, Japan.
Ann Vasc Dis. 2020 Jun 25;13(2):151-157. doi: 10.3400/avd.oa.20-00009.
: Inflammatory response is central to pathogenesis of abdominal aortic aneurysm (AAA). Recently, we reported that Syk, a signaling molecule in inflammatory cells, promotes AAA development in a mouse model. In this study, we aimed to investigate the role of Syk in human AAA pathogenesis. We obtained human AAA wall samples during open surgical aortic repair at Kurume University Hospital. Immunohistochemical analyses of AAA samples were performed for Syk activation and cell type markers. Ex vivo culture of human AAA tissue was utilized to evaluate the effect of P505-15, a Syk inhibitor, on secretions of interleukin-6 (IL-6) and matrix metalloproteinases (MMPs). : Immunohistochemical analysis showed infiltration of B cells, T cells, and macrophages in AAA samples. Syk activation was localized mainly in B cells and part of macrophages. AAA tissue in culture secreted IL-6, MMP-9, and MMP-2 without any stimulation. The unstimulated secretions of IL-6, MMP-9, and MMP-2 were insensitive to P505-15. Secretions of IL-6 and MMP-9 were enhanced by exogenous normal human immunoglobulin G (IgG), which was suppressed by P505-15, whereas secretion of MMP-2 was insensitive to IgG or P505-15. : These results demonstrate an important role of Syk for IgG-dependent inflammatory response in human AAA.
炎症反应是腹主动脉瘤（AAA）发病机制的核心。最近，我们报道了炎症细胞中的信号分子Syk在小鼠模型中促进AAA的发展。在本研究中，我们旨在探讨Syk在人类AAA发病机制中的作用。我们在久留米大学医院进行开放性手术主动脉修复时获取了人类AAA壁样本。对AAA样本进行免疫组织化学分析，检测Syk激活情况和细胞类型标志物。利用人类AAA组织的体外培养来评估Syk抑制剂P505 - 15对白细胞介素 - 6（IL - 6）和基质金属蛋白酶（MMPs）分泌的影响。免疫组织化学分析显示，AAA样本中有B细胞、T细胞和巨噬细胞浸润。Syk激活主要定位于B细胞和部分巨噬细胞。培养中的AAA组织在无任何刺激的情况下分泌IL - 6、MMP - 9和MMP - 2。IL - 6、MMP - 9和MMP - 2的基础分泌对P505 - 15不敏感。外源性正常人免疫球蛋白G（IgG）可增强IL - 6和MMP - 9的分泌，P505 - 15可抑制这种增强作用，而MMP - 2的分泌对IgG或P505 - 15不敏感。这些结果表明Syk在人类AAA的IgG依赖性炎症反应中起重要作用。
