Kummer J A, Abbink J J, de Boer J P, Roem D, Nieuwenhuys E J, Kamp A M, Swaak T J, Hack C E
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Arthritis Rheum. 1992 Aug;35(8):884-93. doi: 10.1002/art.1780350806.
Intraarticular activation of the fibrinolytic system has been suspected to occur in patients with arthritis. We undertook the present study to investigate the relation of this activation to clinical symptoms, and the molecular pathways involved.
We quantitatively assessed levels of plasmin-alpha 2-antiplasmin (PAP) complexes in synovial fluid (SF) from 25 patients with rheumatoid arthritis (RA), 7 with seronegative spondylarthropathy (SSA), and 10 with osteoarthritis (OA), and conducted an analysis to determine the plasminogen-activating pathway via which these complexes were generated. In addition, we studied the relationship of intraarticular fibrinolysis to clinical and biochemical parameters.
All patients studied had increased SF levels of PAP complexes. Levels in patients with RA and SSA were slightly higher than those in patients with OA. These complexes were probably formed by activation of urokinase-type plasminogen activator (u-PA), and not tissue-type plasminogen activator (t-PA), since SF levels of both u-PA antigen and u-PA-plasminogen activator inhibitor (PAI) complexes were increased in 27 of the 42 patients. Conversely, SF levels of t-PA were below normal in all but 1 patient. In some patients, activation of factor XII presumably also contributed to plasminogen activation in SF, since levels of factor XIIa-C1 inhibitor in SF were increased in 8 of the 42 patients and correlated, as did u-PA-PAI levels, with levels of PAP complexes. Several of the parameters of fibrinolysis in SF, particularly u-PA antigen and u-PA-PAI-1 complexes, were found to correlate with clinical and biochemical parameters.
Our results suggest that plasminogen is frequently activated in the joints of patients with inflammatory or noninflammatory arthropathy and that this activation mainly occurs via a u-PA-, and in some cases also via a factor XII-, dependent pathway. The possible relation of this activation process to stimulation of synovial cells by cytokines is discussed.
关节炎患者被怀疑存在关节内纤维蛋白溶解系统的激活。我们开展本研究以调查这种激活与临床症状的关系以及所涉及的分子途径。
我们定量评估了25例类风湿关节炎（RA）患者、7例血清阴性脊柱关节病（SSA）患者和10例骨关节炎（OA）患者滑液（SF）中纤溶酶-α2-抗纤溶酶（PAP）复合物的水平，并进行分析以确定这些复合物产生所经由的纤溶酶原激活途径。此外，我们研究了关节内纤维蛋白溶解与临床和生化参数的关系。
所有研究患者的SF中PAP复合物水平均升高。RA和SSA患者的水平略高于OA患者。这些复合物可能是由尿激酶型纤溶酶原激活物（u-PA）而非组织型纤溶酶原激活物（t-PA）激活形成的，因为42例患者中有27例的u-PA抗原和u-PA-纤溶酶原激活物抑制剂（PAI）复合物的SF水平均升高。相反，除1例患者外，所有患者的t-PA的SF水平均低于正常。在一些患者中，因子XII的激活可能也促成了SF中纤溶酶原的激活，因为42例患者中有8例的SF中因子XIIa-C1抑制剂水平升高，且与u-PA-PAI水平一样，与PAP复合物水平相关。SF中纤维蛋白溶解的几个参数，特别是u-PA抗原和u-PA-PAI-1复合物，被发现与临床和生化参数相关。
我们的结果表明，在炎性或非炎性关节病患者的关节中，纤溶酶原经常被激活，且这种激活主要通过u-PA依赖性途径发生，在某些情况下也通过因子XII依赖性途径发生。讨论了这种激活过程与细胞因子对滑膜细胞刺激的可能关系。
