Haywood L, McWilliams D F, Pearson C I, Gill S E, Ganesan A, Wilson D, Walsh D A
University of Nottingham/City Hospital, Clinical Sciences Building, Hucknall Road, Nottingham NG5 1PB, UK.
Arthritis Rheum. 2003 Aug;48(8):2173-7. doi: 10.1002/art.11094.
To quantify the relationship between inflammation and angiogenesis in synovial tissue from patients with osteoarthritis (OA).
Hematoxylin and eosin staining and histologic grading for inflammation were performed for 104 patients who met the American College of Rheumatology criteria for OA and had undergone total joint replacement or arthroscopy. A purposive sample of synovial specimens obtained from 70 patients was used for further analysis. Vascular endothelium, endothelial cell (EC) proliferating nuclei, macrophages, and vascular endothelial growth factor (VEGF) were detected by immunohistochemical analysis. Angiogenesis (EC proliferation, EC fractional area), macrophage fractional area, and VEGF immunoreactivity were measured using computer-assisted image analysis. Double immunofluorescence histochemical analysis was used to determine the cellular localization of VEGF. Radiographic scores for joint space narrowing and osteophyte formation in the knee were also assessed.
Synovial tissue samples from 32 (31%) of 104 patients with OA showed severe inflammation; thickened intimal lining and associated lymphoid aggregates were often observed. The EC fractional area, EC proliferation, and VEGF immunoreactivity all increased with increasing histologic inflammation grade and increasing macrophage fractional area. In the synovial intimal lining, VEGF immunoreactivity was localized to macrophages and increased with increasing EC fractional area and angiogenesis. No inflammation or angiogenic indices were significantly correlated with radiographic scores.
Inflammation and angiogenesis in the synovium are associated with OA. The angiogenic growth factor VEGF generated by the inflamed synovium may promote angiogenesis, thereby contributing to inflammation in OA.
量化骨关节炎（OA）患者滑膜组织中炎症与血管生成之间的关系。
对104例符合美国风湿病学会OA标准且接受全关节置换或关节镜检查的患者进行苏木精-伊红染色及炎症组织学分级。从70例患者中获取的滑膜标本的有目的样本用于进一步分析。通过免疫组织化学分析检测血管内皮、内皮细胞（EC）增殖核、巨噬细胞和血管内皮生长因子（VEGF）。使用计算机辅助图像分析测量血管生成（EC增殖、EC分数面积）、巨噬细胞分数面积和VEGF免疫反应性。采用双重免疫荧光组织化学分析确定VEGF的细胞定位。还评估了膝关节关节间隙狭窄和骨赘形成的放射学评分。
104例OA患者中有32例（31%）的滑膜组织样本显示严重炎症；常观察到内膜增厚及相关淋巴样聚集物。EC分数面积、EC增殖和VEGF免疫反应性均随组织学炎症分级增加及巨噬细胞分数面积增加而升高。在滑膜内膜中，VEGF免疫反应性定位于巨噬细胞，并随EC分数面积和血管生成增加而升高。炎症或血管生成指标与放射学评分均无显著相关性。
滑膜中的炎症和血管生成与OA相关。炎症滑膜产生的血管生成生长因子VEGF可能促进血管生成，从而导致OA中的炎症。
