Role of the tissue factor pathway in synovial inflammation
Role of the tissue factor pathway in synovial inflammation
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DOI：
10.1002/art.10869
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发表时间：
2003-03-01
影响因子：
--
通讯作者：
So, A
中科院分区：
文献类型：
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作者：
Busso, N;Morard, C;So, A
Objective.临床和实验证据表明，关节炎关节中的血管外纤维蛋白沉积是显著且有害的。本研究旨在探讨组织因子（TF）及其抑制剂TF途径抑制剂（TFPI）在关节炎中的作用。对10例类风湿性关节炎（RA）和12例骨关节炎（OA）患者的滑膜组织标本进行炎症和纤维蛋白含量的组织学评分。TF和TFPI水平在抗原性和功能性上进行测定。程度. TF信使RNA（mRNA）水平测定使用RNA酶保护试验。通过全身给予活性位点封闭的活化因子VIIa（FVIIai）来评估TF抑制在小鼠抗原诱导的关节炎（AIA）中的作用。与OA患者相比，RA患者滑膜的功能性TF活性显著增加。相比之下，TF mRNA和TF抗原水平在这两组之间没有观察到差异。这种差异可以用TPPI来解释，因为我们观察到TF活性和TFPI活性之间呈负相关。两者之间有显著性差异。RA组和OA组在滑膜炎症方面差异无统计学意义，RA组的炎症反应更明显。最重要的是，TF活性与纤维蛋白（P = 0.024）和组织学炎症（P = 0.03）评分相关。在AIA中，在关节炎的第9天，FVIIai对TF诱导的凝血的抑制导致滑膜厚度降低和关节软骨损伤减少，尽管对照组和治疗组小鼠之间仅后者差异达到显著性（P < 0.04）。最后，在FVIIai治疗的小鼠中，凝血酶原时间和关节内纤维蛋白沉积之间存在强烈的负相关性。我们的研究结果表明，TF在关节炎滑膜组织中的表达有利于血管外凝血，并可能在RA的炎症中发挥作用。在这种情况下，TF抑制剂可能具有治疗价值。
Objective. Clinical and experimental evidence suggests that extravascular fibrin deposition in arthritic joints is prominent and deleterious. The aim of this study was to investigate the contributions of tissue factor (TF) and its inhibitor, TF pathway inhibitor (TFPI), in arthritis.Methods. Synovial tissue specimens obtained from 10 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthritis (OA) were scored histologically for inflammation and fibrin content. TF and TFPI levels were assayed at antigenic and functional. levels. TF messenger RNA (mRNA) levels were determined using RNase protection assays. The effect of TF inhibition in murine antigen-induced arthritis (AIA) was assessed by administering systemically active site-blocked activated factor VIIa (FVIIai).Results. Functional TF activity was significantly increased in synovial membranes from RA patients compared with those from OA patients. In contrast, no difference in TF mRNA and TF antigenic levels was observed between these 2 groups. This discrepancy can be accounted for by TPPI, because we observed a negative correlation between TF activity and TFPI activity. There was a significant difference between the. RA and OA groups in terms of synovial inflammation, with more inflammation observed in the RA group. Most importantly, TF activity was associated with fibrin (P = 0.024) and with histologic inflammation (P = 0.03) scores. In AIA, inhibition of TF-induced coagulation by FVIIai led, on day 9 of arthritis, to decreased synovial thickness and decreased articular cartilage damage, although only the latter difference between controls and treated mice reached significance (P < 0.04). Finally, in FVIIai-treated mice, there was a strong negative association between the prothrombin time and intraarticular fibrin deposition.Conclusion. Our results show that TF expression in arthritic synovial tissue favors extravascular coagulation and may play a role in inflammation in RA. In this context, TF inhibitors may be of therapeutic value.