APOPTOSIS IN RHEUMATOID-ARTHRITIS SYNOVIUM
APOPTOSIS IN RHEUMATOID-ARTHRITIS SYNOVIUM
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DOI：
10.1172/jci118202
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发表时间：
1995-09-01
影响因子：
15.9
通讯作者：
ZVAIFLER, NJ
中科院分区：
文献类型：
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作者：
FIRESTEIN, GS;YEO, M;ZVAIFLER, NJ
研究了 RA 滑膜组织 (ST)，以确定细胞凋亡是否以及在何处发生原位，从 5 个 RA 和 1 个骨关节炎 ST 样本中提取基因组 DNA。琼脂糖凝胶电泳证明了每个组织细胞凋亡的 DNA 梯特征，原位末端标记 (ISEL) 用于识别与冰冻切片中细胞凋亡一致的 DNA 链断裂。 ISEL检测12例RA和4例骨关节炎ST均呈阳性，但4例正常组织中仅2例呈阳性，凋亡细胞主要位于滑膜内层，部分亚层细胞也呈阳性，但淋巴聚集体染色明显缺失，免疫组化和ISEL联合显示DNA链断裂的内层细胞主要为巨噬细胞，但也标记了一些成纤维细胞样细胞。带有片段化 DNA 的亚衬细胞包括巨噬细胞和成纤维细胞，但表达大量 bcl-2 的淋巴聚集体中的 T 细胞幸免于难。使用 ISEL 评估培养的成纤维细胞样滑膜细胞中的 DNA 链断裂，放线菌素 D、抗 fas 抗体、IL-1 和 TNF-α 可以诱导细胞凋亡，但 TFN-γ 不能诱导细胞凋亡。使用流式细胞术也在成纤维样滑膜细胞上检测到Fas表达，因此，关节炎患者滑膜中发生DNA链断裂。细胞因子调节这一过程，RA 中的细胞因子谱（高 IL-1/TNP；低 IFN-gamma）以及局部氧化损伤可能有利于诱导细胞凋亡。
RA synovial tissue (ST) was studied to determine if and where apoptosis occurs in situ, Genomic DNA was extracted from 5 RA and 1 osteoarthritis ST samples. Agarose gel electrophoresis demonstrated DNA ladders characteristic for apoptosis from each tissue, In situ end labeling (ISEL) was used to identify DNA strand breaks consistent with apoptosis in frozen sections. 12 RA and 4 osteoarthritis ST were studied by ISEL and all were positive, but only 2 of 4 normal tissues were positive, The primary location of apoptotic cells was the synovial lining, Some sublining cells were also positive, but lymphoid aggregate staining was conspicuously absent, Immunohistochemistry and ISEL were combined and showed that the lining cells with DNA strand breaks were mainly macrophages, although some fibroblastlike cells were also labeled. Sublining cells with fragmented DNA included macrophages and fibroblasts, but T cells in lymphoid aggregates, which expressed large amounts of bcl-2, were spared. DNA strand breaks in cultured fibroblastlike synoviocytes was assessed using ISEL, Apoptosis could be induced by actinomycin D, anti-fas antibody, IL-1, and TNF-alpha but not by TFN-gamma. Fas expression was also detected on fibroblast-like synoviocytes using flow cytometry, Therefore, DNA strand breaks occur in synovium of patients with arthritis. Cytokines regulate this process, and the cytokine profile in RA (high IL-1/TNP; low IFN-gamma) along with local oxidant injury might favor induction of apoptosis.