CYTOKINES IN CHRONIC INFLAMMATORY ARTHRITIS .2. GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN RHEUMATOID SYNOVIAL EFFUSIONS
CYTOKINES IN CHRONIC INFLAMMATORY ARTHRITIS .2. GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN RHEUMATOID SYNOVIAL EFFUSIONS
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DOI：
10.1172/jci113971
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发表时间：
1989-03-01
影响因子：
15.9
通讯作者：
ZVAIFLER, NJ
中科院分区：
文献类型：
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作者：
XU, WD;FIRESTEIN, GS;ZVAIFLER, NJ
用液体培养技术对23例滑液(21例炎症性关节疾病和2例非炎症性滑液)和2例类风湿关节炎(RA)滑膜组织培养上清液进行了集落刺激因子(CSF)检测。比较滑液、滑膜组织培养上清液和重组粒细胞-巨噬细胞集落刺激因子(RGM-CSF)对人外周血巨噬细胞耗竭的非T细胞的增殖反应。在长期培养(15d)中形成的细胞聚集体对于每种施加剂都是相似的，由巨噬细胞、嗜酸性粒细胞和大母细胞组成。氚胸苷掺入与RGM-CSF的浓度成正比，并伴随着培养中形成的细胞聚集体的数量和大小的增加。在炎症性SF中可以观察到脑脊液的活性，在RA存在的情况下(n=15)，胸腺嘧啶核苷摄取量为3,501+/-1,140 cpm，而在非RA炎症性SF(n=7)和介质(n=6)中分别为1,985+/-628(P<0.05)和583+/-525(P<0.01)。当样品被稀释时，对RA SF的增殖反应通常更明显，因为在较高浓度时RA SF是抑制的。两个RA SF用Sephadex G100柱层析分离，在70-100kD的MR组分中检测到较低水平的CSF活性，但在20-24-KD组分中检测到主要的CSF活性。用兔抗GM-CSF多克隆抗体可消除RGM-CSF和RA SF的刺激活性。最后，一种特异的放射免疫分析在另外3个RA滑膜组织的培养上清液中发现了显著水平的GM-CSF(40-140U/ml)。这些数据记录了类风湿性滑膜炎局部产生的GM-CSF，并首次在疾病活动部位描述了这种细胞因子。
A liquid culture technique was used to study 23 synovial fluids (SF) (21 from inflammatory joint diseases and 2 noninflammatory SF) and supernatants of two cultured rheumatoid arthritis (RA) synovial tissues for colony-stimulating factor (CSF). The proliferative responses of human peripheral blood macrophage-depleted non-T cells treated with synovial fluids, supernatants of synovial tissue explants, and recombinant granulocyte-macrophage (rGM)-CSF were compared. Aggregates of cells that formed in long-term cultures (15 d) were similar for each applied agent and consisted of macrophages, eosinophils, and large blasts. Tritiated thymidine incorporation was proportional to the concentration of rGM-CSF and was accompanied by an increase in number and size of cellular aggregates formed in the cultures. CSF activity was observed in inflammatory SF, with tritiated thymidine uptake of 3,501 +/- 1,140 cpm in the presence of RA samples (n = 15) compared to 1,985 +/- 628 for non-RA inflammatory SF (n = 7) (P less than 0.05) and 583 +/- 525 for medium (n = 6) (P less than 0.01). The proliferative response to RA SF was often more apparent when the samples were diluted, because at higher concentrations the RA SF was inhibitory. Two RA SF were fractionated by Sephadex G100 column chromatography; low levels of CSF activity were detected in fractions corresponding to Mr of 70-100 kD, but the major CSF activity was found in the 20-24-kD fractions. A polyclonal rabbit anti-GM-CSF antibody eliminated the stimulating activity from both rGM-CSF and RA SF. Finally, a specific RIA identified significant levels of GM-CSF (40-140 U/ml) in the culture supernatants of 3 additional RA synovial tissues. These data document the local production of GM-CSF in rheumatoid synovitis and are the first description of this cytokine at a site of disease activity.Images