Nordstrom D, Lindy O, Konttinen Y T, Lauhio A, Sorsa T, Friman C, Pettersson T, Santavirta S
Department of Medicine, Helsinki University Central Hospital, Finland.
Clin Rheumatol. 1996 Jan;15(1):35-41. doi: 10.1007/BF02231682.
The purpose of the study was to evaluate the involvement of serine proteinases cathepsin G and elastase on pathomechanisms in synovial fluid (SF) of patients with reactive (ReA) and rheumatoid, (RA) arthritis. Cathepsin G, elastase, and their endogenous inhibitors alpha1-antichymotrypsin (alpha1-ACT) and alpha1-proteinase inhibitor (alpha1-PI) were identified immunohistochemically from SF and peripheral blood (PB) of patients with ReA and RA. Cathepsin G and elastase activities in SF and PB were measured spectrophotometrically. Dot-immunostaining was used to identify cathepsin G, elastase, but also alpha1-ACT and alpha1-PI from SF and PB. Cathepsin G and elastase-like activities (IU/I) were slightly elevated in ReA SF compared to the corresponding peripheral blood values (11.4 +/- 9.2 vs 4.8 +/- 1.7, NS, and 5.1 +/- 2.8 vs 2.3 +/- 2.2, NS), which was similar to what was seen in RA (16.4 +/- 6.2 vs 0.53 +/- 0.4, p < 0.05, and 6.51 +/- 1.8 vs 1.22 +/- 0.58, p < 0.05). Although some samples did not contain cathepsin G and/or elastase-like activities, all samples contained immunoreactive enzyme, but also alpha1-ACT and alpha1-PI. In ReA SF, in contrast to monocytes, all polymorphonuclear (PMN) cells contained cathepsin G and elastase. Cathepsin G and elastase activities correlated with each other (r = 0.78, p < 0.05) suggesting PMN / primary granules as their likely source. There was a closer association between the cathepsin G or elastase and SF leukocyte count in ReA than in RA. In ReA and RA SF elevated cathepsin G and elastase activities are detected compared to activity levels in PB suggesting local production mainly from PMNs. The co-existence of highly cellular SF and cathepsin G and elastase activity in the documented presence of endogenous inhibitors in ReA SF together with the, known, usually self-remitting clinical course of ReA, suggest a brisk and even exaggerated local PMN serine proteinase release; sparing of joints does not seem to be due to lack or inhibition of PMN responses but rather to a successful down-regulation or cessation of the responses initially elicited.
本研究的目的是评估丝氨酸蛋白酶组织蛋白酶G和弹性蛋白酶在反应性关节炎（ReA）和类风湿关节炎（RA）患者滑液（SF）病理机制中的作用。通过免疫组织化学方法从ReA和RA患者的滑液和外周血（PB）中鉴定出组织蛋白酶G、弹性蛋白酶及其内源性抑制剂α1-抗糜蛋白酶（α1-ACT）和α1-蛋白酶抑制剂（α1-PI）。采用分光光度法测定滑液和外周血中组织蛋白酶G和弹性蛋白酶的活性。采用斑点免疫染色法从滑液和外周血中鉴定组织蛋白酶G、弹性蛋白酶，以及α1-ACT和α1-PI。与相应外周血值相比，ReA滑液中组织蛋白酶G和弹性蛋白酶样活性（IU/I）略有升高（11.4±9.2对4.8±1.7，无显著性差异；5.1±2.8对2.3±2.2，无显著性差异），这与RA患者的情况相似（16.4±6.2对0.53±0.4，p<0.05；6.51±1.8对1.22±0.58，p<0.05）。尽管一些样本不含有组织蛋白酶G和/或弹性蛋白酶样活性，但所有样本均含有免疫反应性酶，以及α1-ACT和α1-PI。在ReA滑液中，与单核细胞不同，所有多形核（PMN）细胞均含有组织蛋白酶G和弹性蛋白酶。组织蛋白酶G和弹性蛋白酶活性相互相关（r=0.78，p<0.05），提示PMN/初级颗粒可能是其来源。与RA相比，ReA中组织蛋白酶G或弹性蛋白酶与滑液白细胞计数之间的关联更为密切。与外周血中的活性水平相比，在ReA和RA滑液中检测到组织蛋白酶G和弹性蛋白酶活性升高，提示主要由PMN局部产生。在记录到的ReA滑液中存在内源性抑制剂的情况下，高细胞性滑液与组织蛋白酶G和弹性蛋白酶活性并存，以及ReA通常的自限性临床病程，提示局部PMN丝氨酸蛋白酶释放活跃甚至过度；关节未受累似乎不是由于PMN反应缺乏或受到抑制，而是由于最初引发的反应成功下调或停止。
