Nozaki Toshiko, Takahashi Kyoko, Ishii Osamu, Endo Sachio, Hioki Kyoji, Mori Toshihito, Kikukawa Tadahiro, Boumpas Dimitrios T, Ozaki Shoichi, Yamada Hidehiro
St. Marianna University School of Medicine, Kawasaki, Japan.
Arthritis Rheum. 2007 Sep;56(9):2875-85. doi: 10.1002/art.22849.
To establish an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue (ST).
Inflammatory cells that infiltrated pannus tissue from patients with rheumatoid arthritis (RA) were collected without enzyme digestion, and designated as ST-derived inflammatory cells. Single-cell suspensions of ST-derived inflammatory cells were cultured in medium alone. Levels of cytokines produced in culture supernatants were measured using enzyme-linked immunosorbent assay kits. ST-derived inflammatory cells were transferred into the joints of immunodeficient mice to explore whether these cells could develop pannus. CD14 and CD2 cells were depleted by negative selection.
Culture of ST-derived inflammatory cells from 92 of 111 patients with RA resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks. Ex vivo tissue contained fibroblasts, macrophages, T cells, and tartrate-resistant acid phosphatase-positive multinucleated cells. On calcium phosphate-coated slides, ST-derived inflammatory cell cultures showed numerous resorption pits. ST-derived inflammatory cell cultures continuously produced matrix metalloproteinase 9 and proinflammatory cytokines associated with osteoclastogenesis, such as tumor necrosis factor alpha, interleukin-8, and macrophage colony-stimulating factor. More importantly, transferring ST-derived inflammatory cells into the joints of immunodeficient mice resulted in the development of pannus tissue and erosive joint lesions. Both in vitro development and in vivo development of pannus tissue by ST-derived inflammatory cells were inhibited by depleting CD14-positive, but not CD2-positive, cells from ST-derived inflammatory cells.
These findings suggest that overgrowth of inflammatory cells from human rheumatoid synovium simulates the development of pannus. This may prove informative in the screening of potential antirheumatic drugs.
建立血管翳的体外细胞模型，即人类滑膜组织（ST）的异常过度生长模型。
从类风湿关节炎（RA）患者的血管翳组织中收集浸润的炎性细胞，无需酶消化，将其命名为ST来源的炎性细胞。将ST来源的炎性细胞单细胞悬液单独培养于培养基中。使用酶联免疫吸附测定试剂盒测量培养上清液中产生的细胞因子水平。将ST来源的炎性细胞转移至免疫缺陷小鼠的关节中，以探究这些细胞是否能形成血管翳。通过阴性选择去除CD14和CD2细胞。
111例RA患者中92例的ST来源炎性细胞培养在4周内导致体外炎性组织的自发重建。体外组织包含成纤维细胞、巨噬细胞、T细胞和抗酒石酸酸性磷酸酶阳性的多核细胞。在磷酸钙包被的载玻片上，ST来源的炎性细胞培养物显示出大量吸收凹坑。ST来源的炎性细胞培养物持续产生基质金属蛋白酶9和与破骨细胞生成相关的促炎细胞因子，如肿瘤坏死因子α、白细胞介素-8和巨噬细胞集落刺激因子。更重要的是，将ST来源的炎性细胞转移至免疫缺陷小鼠的关节中导致血管翳组织和侵蚀性关节病变的形成。从ST来源的炎性细胞中去除CD14阳性而非CD2阳性细胞可抑制ST来源的炎性细胞在体外和体内形成血管翳组织。
这些发现表明，人类类风湿滑膜炎性细胞的过度生长模拟了血管翳的形成。这可能在潜在抗风湿药物的筛选中具有参考价值。
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