Presence of cyclophilin A in synovial fluids of patients with rheumatoid arthritis.
Presence of cyclophilin A in synovial fluids of patients with rheumatoid arthritis.
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DOI：
10.1084/jem.185.5.975
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发表时间：
1997-03-03
期刊：
影响因子：
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通讯作者：
Peichl P
中科院分区：
文献类型：
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作者：
Billich A;Winkler G;Aschauer H;Rot A;Peichl P
亲环蛋白被认为是炎症过程中产生的白细胞趋化因子。因此，我们在类风湿性关节炎（RA）患者的滑膜液（SF）中寻找亲环蛋白的存在。测定了26例RA患者和5例膝关节骨性关节炎（OA）患者膝关节穿刺后SF中肽基脯氨酸顺式反式异构酶活性（PPIase）。在RA患者的SF中检测到PPIase，而在OA患者的样本中未检测到PPIase。酶活性对环孢素A的抑制作用敏感（IC50 = 28 ~ 50 nM）。根据酶活性估计，sf衍生的亲环蛋白浓度在11 ~ 705 nM范围内。SF中亲环蛋白的存在与疾病相关；其浓度与SF细胞数相关（r = 0.91, P <0.0001），与细胞浸润中性粒细胞百分比相关，且在关节肿胀越严重的情况下越高。在部分纯化的RA患者SF制剂的免疫印迹中，一个~ 18-kD蛋白带与识别亲环蛋白A和B的多克隆抗体反应，但与亲环蛋白B特异性抗体不反应。该蛋白的测序揭示了nh2末端氨基酸与人类亲环蛋白A的同源性。这一发现是出乎意料的，因为通常认为亲环蛋白B而不是A是分泌的亚型。亲环蛋白A的存在被限制在细胞质中。我们的数据支持亲环蛋白可能作为细胞因子参与炎症性疾病发病机制的假设。除了已知的药物免疫抑制作用外，这可能为环孢素a治疗类风湿性关节炎的有效性提供了可能的解释。
Cyclophilins have been suggested to act as leukocyte chemotactic factors produced in the course of inflammation. Therefore we looked for the presence of cyclophilins in the synovial fluids (SF) from patients with rheumatoid arthritis (RA). Peptidyl prolyl cis–trans isomerase activity (PPIase) was measured in SF from knee punctures of 26 patients with RA and five patients with knee osteoarthritis (OA). PPIase was detected in SF from RA patients, but not in samples from OA patients. Enzyme activity was sensitive to inhibition by cyclosporin A (IC50 = 28–50 nM). Estimated concentrations of the SF-derived cyclophilin based on the enzyme activity were in the range of 11 to 705 nM. The presence of cyclophilin in the SF showed disease correlation; its concentration correlated with the number of cells in the SF (r = 0.91, P <0.0001) and with the percentage of neutrophils in the cellular infiltrate and was higher in more acute cases of joint swelling. In immunoblots of partially purified preparations of SF from RA patients, an ∼18-kD protein band reacted with polyclonal antibodies that recognize cyclophilin A and B, but not with antibodies specific for cyclophilin B. Sequencing of this protein revealed identity of the NH2-terminal amino acids with those of human cyclophilin A. The finding is unexpected since cyclophilin B rather than A is generally regarded as the secreted isoform, the presence of cyclophilin A being confined to the cytoplasm. Our data support the hypothesis that cyclophilins may contribute to the pathogenesis of inflammatory diseases, possibly by acting as cytokines. This may offer a possible explanation of the effectiveness of cyclosporin A in RA, in addition to the known immunosuppressive effects of the drug.