Study of the mechanism involved in angiogenesis and synovial cell proliferation in human synovial tissues of patients with rheumatoid arthritis using SCID mice
Study of the mechanism involved in angiogenesis and synovial cell proliferation in human synovial tissues of patients with rheumatoid arthritis using SCID mice
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DOI：
10.1097/01.lab.0000022220.44511.40
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发表时间：
2002-08-01
影响因子：
5
通讯作者：
Yoshino, S
中科院分区：
文献类型：
--
作者：
Nagashima, M;Tanaka, H;Yoshino, S
为了检查滑膜细胞增殖是否是由于血管生成，我们研究了滑膜细胞增殖的抑制和血管生成抑制剂TNP-470在人滑膜组织中的关系。将人滑膜组织植入SCID小鼠（SCID-HuAg小鼠）的背部。将16只小鼠分成两组，每组8只小鼠：未处理组（媒介物组）和通过皮下注射接受10 mg/kg体重剂量的TNP-470处理组。在溶剂组中，血管和滑膜衬里细胞的数量明显增加，但在TNP-470组中，滑膜衬里细胞的数量明显减少，几乎检测不到血管。免疫组化显示，抗增殖细胞核抗原（PCNA）单克隆抗体阳性的细胞在滑膜衬里细胞和滑膜组织的内皮细胞中大量存在。载体组的内皮细胞中存在大量抗CD 34多克隆抗体染色阳性的细胞，但在TNP-470组中几乎检测不到这些阳性染色的细胞。载体组的PCNA阳性率为0.64 +/-0.019，而TNP-470组为0.199 +/-0.007。溶剂组中抗CD 34多克隆抗体染色阳性的细胞数为242 +/- 13.4/10个显微镜视野，TNP-470组中为153 +/- 6.73/10个显微镜视野。抗小鼠CD 31单克隆抗体染色阳性的细胞主要位于滑膜衬里层，但在人滑膜组织中侵入滑膜下衬里层。另一方面，抗人CD 31 mAb染色阳性的细胞主要位于滑膜下衬里层。基于TNP-470处理抑制血管生成和滑膜细胞增殖的结果，我们发现内皮细胞增殖依赖于血管生成。
To examine whether synovial cell proliferation is due to angiogenesis, we studied the relationship between the inhibition of synovial cell proliferation and an angiogenesis inhibitor, TNP-470, in human synovial tissues. Human synovial tissues were implanted into the back of SCID mice (SCID-HuAg mice). Sixteen mice were divided into two groups of eight mice each: the untreated group (vehicle group) and the TNP-470-treated group that received a dose of 10 mg/kg body weight by subcutaneous injection. The number of blood vessels and synovial lining cells clearly increased in the vehicle group, but the number of synovial lining cells clearly decreased and the blood vessels were hardly detected in the TNP-470 group. Immunohistochemically, cells that stained positively for the anti-proliferating cell nuclear antigen (PCNA) mAb were abundant in synovial lining cells and endothelial cells in synovial tissues. Cells that stained positively for the anti-CD34 polyclonal antibody were abundant in the endothelial cells in the vehicle group, but these positively stained cells were hardly detected in the TNP-470 group. The PCNA positivity ratio in the vehicle group was 0.64 +/- 0.019, whereas that in the TNP-470 group was 0.199 +/- 0.007. The numbers of cells that stained positively for anti-CD34 polyclonal antibody were 242 +/- 13.4 in the vehicle group and 153 +/- 6.73 in the TNP-470 group per 10 microscopic fields. Cells that stained positively for anti-mouse CD31 mAb were mainly localized in the synovial lining, but invaded the subsynovial lining layer in human synovial tissues. On the other hand, cells that stained positively for anti-human CD31 mAb were mainly localized in the subsynovial lining layer. We found that endothelial cell proliferation is dependent on angiogenesis based on the result that angiogenesis, and synovial cell proliferation were inhibited by treatment with TNP-470.