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Abnormal Myeloid Lineage Cells Expressing the Difucosyl or Trifucosyl Type 2 Chain in Bone Marrow Cells of Patinets with Severe Rheumatoid Arthritis.

患有严重类风湿性关节炎的患者骨髓细胞中表达二岩藻糖基或三岩藻糖基 2 型链的异常骨髓谱系细胞。

基本信息

批准号：
06454429
负责人：
OCHI Takahiro
金额：
$ 4.16万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

The absolute number of mononuclear cells in the iliac bone marrow was incresed by 3-fold in the rheumatoid arthritis (RA) patients compared with non-RA controls. In contrast, no significant increase of MNC was abserved in the epiphyseal bone marrow or peripheral blood. In lymphocyte subsets, the percentage of HLA-DR+CD8+cells to all CD8 cells in the iliac bone marrow increased significantly in the RA patients compared with the non-RA controls. Abnormal myeloid cells (CD14+CD15+cells) , specific to severe RA,were found to be more concentrated in the iliac bone marrow than in the tibial epiphyseal bone marrow. The production of these abnormal myeloid cells was enhanced by IL-1beta and GM-CSF,but inhibited by T lymphocytes. These abnormal myeloid cells were confirmed to differentiated to polymorphonuclear leukocytes. In patients with severe disease of RA, high levels of IL-1alpha and IL-1beta were found in the cell lysates of MNC and PMN in the epiphyseal bone marrow adjacent to affected joints. Markedly elevated levels of IL-6 and IL-8 were detected in iliac bone marrow serum, and much lower levels were found in the tibial bone marrow and peripheral blood serum. The levels of IL-6 and IL-8 in iliac bone marrow serum showed a close relationship to the extent of synovial proliferation. Stromal cell (nurse cell) line were established from both bone marrow and synovium.These cell lines were shown to have an enhanced ability to support the pre-B-cell lines and to maintain abnormal myeliod cells.

与非 RA 对照组相比，类风湿性关节炎 (RA) 患者的髂骨骨髓中单核细胞的绝对数量增加了 3 倍。相反，在骨骺骨髓或外周血中没有观察到MNC的显着增加。在淋巴细胞亚群中，与非 RA 对照相比，RA 患者髂骨髓中 HLA-DR+CD8+ 细胞占所有 CD8 细胞的百分比显着增加。异常骨髓细胞（CD14+CD15+细胞）是严重RA特有的，被发现在髂骨骨髓中比在胫骨骨骺骨髓中更集中。 IL-1β和GM-CSF可增强这些异常骨髓细胞的产生，但T淋巴细胞会抑制这些细胞的产生。这些异常骨髓细胞被证实分化为多形核白细胞。在患有严重 RA 疾病的患者中，在受影响关节附近的骨骺骨髓中的 MNC 和 PMN 细胞裂解物中发现了高水平的 IL-1α 和 IL-1β。髂骨骨髓血清中IL-6和IL-8水平显着升高，而胫骨骨髓和外周血清中IL-6和IL-8水平显着降低。髂骨骨髓血清中IL-6、IL-8的水平与滑膜增殖程度密切相关。基质细胞（护士细胞）系是从骨髓和滑膜中建立的。这些细胞系被证明具有增强的支持前 B 细胞系和维持异常骨髓细胞的能力。