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Myeloid cell cascade bearing onco-fetal membrane structure found in the involved epiphyseal bone marrow in patients with severe active rheumatoid arthritis

在严重活动性类风湿关节炎患者受累骨骺骨髓中发现具有癌胎膜结构的骨髓细胞级联

基本信息

批准号：
02454345
负责人：
OCHI Takahiro
金额：
$ 4.35万
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：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

Main purpose is to study the role of bone marrow in inducing or persisting poly-arthritis like rheumatoid arthritis. In experimental polyarthritis, pathological changes were seen primarily in bone marrow. Preceding the beginning of synovial proliferation, the cellular development and proliferation of bone marrow cells and the elevation of IL-1 and -6 could be observed in bone marrow. Thus, the role of bone marrow in inducing polyarthritis were impressed.In the persistent severe inflammatory process of RA, some uncontrollable proliferation of a certain type of undifferentiated cells could be accompanied by destruction and disorganization of normal cells. We found an accumulation of abnormal myeloid lineage bearing aberrant carbohydrate membrane structures in the bone marrow of patients with severe active rheumatoid arthritis. Polymorphonuclear leukocytes, mature cells of myeloid lineage, accumulating in these lesions were found to contain unususally high levels of IL-1.We further survey … More ed bone marrow of ilium as a systemic hemopoietic organ. In iliac bone marrow, numbers of each mononuclear cell fractions were highly significantly increased. The increase of activated (HLADR+) CD8 cells were significant. in iliac bone marrow of RA patients with both severe and mild natural course. The increase of myeloid cells in iliac bone marrow was significant in patients with severe destructive disease of RA. The abnormal myeloid cells primarily found in the epiphyseal bone marrow were found to accumulate much more in the iliac bone marrow of patients with severe destructive RA.Cytokines were also surveyed in bone marrows. In the iliac bone marrow of RA patients, elevation of IL-6, and IL-8 were characteristically found. The elevation of these cytokines in peripheral blood were also found, but the levels were much less than those in the iliac bone marrow. Interestingly, the elevation of IL-6, -8 showed close relationships with exacerbation of synovitis in multiple joints.Thus, in RA patients, iliac bone marrow could be a primarily important lesion, and could influence the peripheral blood and epiphyseal bone marrow. We are further surveying the roles of bone marrow in inducing RA. Less

主要目的是研究骨髓在类风湿关节炎等多发性关节炎的诱导或持续中的作用。在实验性多发性关节炎中，病理改变主要见于骨髓。滑膜增生开始前，骨髓细胞发育、增殖及IL-1、-6水平升高。由此可见骨髓在诱导多发性关节炎中的作用。在RA的持续严重炎症过程中，某些类型的未分化细胞的一些不可控增殖可能伴随着正常细胞的破坏和解体。我们发现在严重活动性类风湿关节炎患者的骨髓中积累了异常的骨髓谱系，携带异常的碳水化合物膜结构。在这些病变中积累的多形核白细胞，成熟的髓系细胞被发现含有异常高水平的IL-1。我们进一步研究了髂骨骨髓作为全身造血器官的作用。髂骨髓中各单核细胞分数均显著升高。活化（HLADR+） CD8细胞显著增加。在重度和轻度自然病程的RA患者髂骨髓中。严重破坏性RA患者髂骨髓髓系细胞明显增多。在严重破坏性类风湿性关节炎患者的髂骨髓中，发现主要在骨骺中发现的异常髓样细胞积聚得更多。骨髓细胞因子也被检测。在RA患者的髂骨髓中，IL-6和IL-8的升高是特征性的。外周血中这些细胞因子的升高也被发现，但其水平远低于髂骨髓中的水平。有趣的是，IL-6、-8的升高与多关节滑膜炎的加重密切相关。因此，在RA患者中，髂骨髓可能是主要的重要病变，并可能影响外周血和骨骺骨髓。我们正在进一步研究骨髓在RA诱导中的作用。少