Hasday J D, Bachwich P R, Lynch J P, Sitrin R G
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
Exp Lung Res. 1988;14(2):261-78. doi: 10.3109/01902148809115128.
Tissue fibrin deposition may be an important component of inflammatory reactions. Current evidence suggests that intraalveolar procoagulant (PC) and plasminogen activator (PA) activities may be important determinants of local fibrin turnover in lung injury. In this study, we measured the PC and PA activities in cell-free bronchoalveolar lavage fluid (BALF) obtained from 17 patients with pulmonary sarcoidosis and 12 normal volunteers. Procoagulant activity was assayed by timing clot formation in a one-stage coagulation assay, and plasminogen activator activity was determined by measuring plasminogen-dependent lysis of [125I]fibrin. Mean PC activity in the sarcoidosis group was significantly elevated (102 +/- 25 versus 31.5 +/- 8.1 tissue thromboplastin units/ml; p less than 0.002), with 6 of 17 patient values beyond the 95% confidence limits of normals. These differences were not seen when PC activity was corrected for total protein in BAL. In contrast, PA activity tended to be lower in the sarcoidosis group (0.54 +/- 0.094 versus 0.643 +/- 0.106 Plough units/ml, p less than 0.3), and this difference became significant when PA was normalized to total protein (p less than 0.001). The ratio of procoagulant activity compared to plasminogen activator (PC/PA) was greater in the patients with sarcoidosis than normals (258 +/- 54 versus 40.3 +/- 6.4; p less than 0.001). The PC/PA ratios in 14 of 17 patients exceeded the 95% confidence limits of normals. In the sarcoidosis group, the PC/PA ratio correlated weakly with the number and percentage of lymphocytes retrieved by BAL. The plasminogen activator was a urokinase by molecular weight (53 kDa) and by comparing neutralization of PA activity by antibodies against urokinase and tissue plasminogen activator. The procoagulant was particulate and functioned as a factor X activator comprised of tissue thromboplastin and factor VII. We conclude that in pulmonary sarcoidosis, abnormal expression of procoagulant and plasminogen activator activities in alveolar fluid may favor accumulation of fibrin matrix at inflammatory foci.
组织纤维蛋白沉积可能是炎症反应的一个重要组成部分。目前的证据表明，肺泡内促凝剂（PC）和纤溶酶原激活剂（PA）的活性可能是肺损伤中局部纤维蛋白周转的重要决定因素。在本研究中，我们测量了从17例肺结节病患者和12名正常志愿者获得的无细胞支气管肺泡灌洗液（BALF）中的PC和PA活性。促凝活性通过在一期凝血试验中计时凝块形成来测定，纤溶酶原激活剂活性通过测量[125I]纤维蛋白的纤溶酶原依赖性溶解来确定。结节病组的平均PC活性显著升高（102±25对31.5±8.1组织凝血活酶单位/毫升；p<0.002），17例患者中有6例的值超出正常范围的95%置信限。当对BAL中的总蛋白校正PC活性时，未观察到这些差异。相反，结节病组的PA活性往往较低（0.54±0.094对0.643±0.106普劳单位/毫升，p<0.3），当将PA标准化为总蛋白时，这种差异变得显著（p<0.001）。结节病患者的促凝活性与纤溶酶原激活剂的比值（PC/PA）高于正常对照组（258±54对40.3±6.4；p<0.001）。17例患者中有14例的PC/PA比值超过正常范围的95%置信限。在结节病组中，PC/PA比值与通过BAL回收的淋巴细胞数量和百分比弱相关。通过分子量（53 kDa）以及比较抗尿激酶和组织纤溶酶原激活剂抗体对PA活性的中和作用，确定纤溶酶原激活剂为尿激酶。促凝剂为颗粒状，作为由组织凝血活酶和因子VII组成的因子X激活剂发挥作用。我们得出结论，在肺结节病中，肺泡液中促凝剂和纤溶酶原激活剂活性的异常表达可能有利于纤维蛋白基质在炎症灶处的积聚。
