Macrophages express granzyme B in the lesion areas of atherosclerosis and rheumatoid arthritis

Macrophages express granzyme B in the lesion areas of atherosclerosis and rheumatoid arthritis
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DOI:
10.1016/j.imlet.2007.05.004
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发表时间:
2007-07-31
期刊:
影响因子:
4.4
通讯作者:
Lee, Won-Ha
Lee, Won-Ha
中科院分区:
医学3区
文献类型:
--
作者:
Kim, Won-Jung;Kim, Ho;Lee, Won-Ha

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粒酶 B 是细胞毒性免疫反应的主要介质,在存在的情况下内化时会诱导靶细胞死亡。最近,一些研究关注颗粒酶 B 的另一个作用,即通过降解 ECM 蛋白来重塑细胞外基质 (ECM)。为了研究颗粒酶B在动脉粥样硬化和类风湿性关节炎病变区域的表达模式,我们利用人动脉粥样硬化斑块以及类风湿性关节炎和骨关节炎关节的滑膜组织进行了免疫组织化学和原位杂交分析。在动脉粥样硬化斑块中,巨噬细胞在中膜和内膜之间的边界区域、坏死核心周围区域以及肩部区域等区域表达颗粒酶 B。在类风湿性关节炎关节的滑膜组织中,在大多数细胞为巨噬细胞的内衬层以及巨噬细胞和少量淋巴细胞混合形成弥漫性细胞聚集体的血管周围区域中强烈观察到颗粒酶B的表达。在骨关节炎滑膜中未检测到粒酶 B 阳性细胞。此外,在人巨噬细胞系THP-1中,ECM蛋白或诱导巨噬细胞分化的试剂已诱导颗粒酶B的表达。这些观察结果表明,巨噬细胞应添加到人类炎症性疾病中表达颗粒酶 B 的细胞类型列表中,并且颗粒酶 B 可能在与疾病进展相关的巨噬细胞功能中发挥作用。 (c) 2007 Elsevier B.V. 保留所有权利。
Granzyme B is a major mediator of the cytotoxic immune response by inducing target cell death when internalized in the presence of perform. Recently, several studies have focused on another role of granzyme B, which is extracellular matrix (ECM) remodeling through the degradation of ECM proteins. In order to investigate the expression pattern of granzyme B in the lesion areas of atherosclerosis and rheumatoid arthritis, we performed immunohistochemistry and in situ hybridization analyses using human atherosclerotic plaques and the synovial tissues of rheumatoid arthritic- and osteoarthritic-joints. In atherosclerotic plaques, granzyme B was expressed by macrophages in areas such as the boundary regions between media and intima, areas around necrotic cores, and in shoulder regions. In the synovial tissues of rheumatoid arthritic-joints, the expression of granzyme B was strongly observed in the lining layers where the majority of cells are macrophages and also in perivascular areas where macrophages and a small number of lymphocytes were mixed to form diffuse cellular aggregates. Granzyme B-positive cells were not detected in osteoarthritic synovium. Furthermore, the expression of granzyme B has been induced in the human macrophage cell line, THP- 1, by ECM proteins or agents which induce macrophage differentiation. These observations indicate that macrophages should be added to the list of cell types that express granzyme B in human inflammatory diseases and that granzyme B may play a role in macrophage functions that are associated with disease progression. (c) 2007 Elsevier B.V. All rights reserved.