Single-chain urokinase alone or complexed to its receptor in tetracycline-induced pleuritis in rabbits
Single-chain urokinase alone or complexed to its receptor in tetracycline-induced pleuritis in rabbits
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DOI：
10.1164/rccm.200204-313oc
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发表时间：
2002-10-01
影响因子：
24.7
通讯作者：
Miller, E
中科院分区：
文献类型：
--
作者：
Idell, S;Mazar, A;Miller, E
胸膜内分室可增加血胸或胸膜旁积液的发病率。胸膜内纤维蛋白先于脏壁胸膜粘连。我们推测，单链尿激酶纤溶酶原激活剂单独或结合到其受体可以防止这些粘连，通过他们的相对抵抗局部抑制纤溶酶原激活剂抑制剂。我们发现，重组人单链尿激酶结合兔胸膜间皮瘤细胞或肺成纤维细胞的动力学类似于人类细胞（kD约5 nM）。受体结合的纤溶酶在四环素诱导的胸膜损伤的兔的胸腔积液中保持体外纤溶活性超过24小时。在胸膜内四环素给药后24和48小时给予胸膜内单链尿激酶的家兔中（n = 10只动物），粘连得到预防，而受体复合物形式（n = 12）与溶媒/四环素给药的家兔相比减轻了粘连（n = 22，两种情况下p均小于或等于0.005）。复合体中的粘连多于单链尿激酶组（p = 0.02）。四环素给药后72小时，胸腔液中残留有干预剂的抗原性证据，但无功能性证据。两种介入剂均未导致局部或全身出血。数据表明，单链尿激酶抑制，而赖氨酸受体复合物衰减，在四环素诱导的胸膜损伤的兔粘连形成。
Intrapleural loculation can increase morbidity in hemothoraces or parapneumonic effusions. Intrapleural fibrin precedes visceral-parietal pleural adhesions. We speculated that single-chain urokinase plasminogen activator alone or bound to its receptor could prevent these adhesions by their relative resistance to local inhibition by plasminogen activator inhibitors. We found that recombinant human single-chain urokinase-bound rabbit pleural mesothelial cells or lung fibroblasts with kinetics similar to that reported for human cells (kD of approximately 5 nM). The receptor-bound fibrinolysin maintained in vitro fibrinolytic activity in the presence of pleural fluids from rabbits with tetracycline-induced pleural injury over 24 hours. In rabbits given intrapleural single-chain urokinase 24 and 48 hours after intrapleural tetracycline (n = 10 animals), adhesions were prevented, whereas the receptor-complexed form (n = 12) attenuated adhesions versus vehicle/tetracycline-treated rabbits (n = 22, p less than or equal to 0.005 in both cases). There were more adhesions in the complex than the single-chain urokinase group (p = 0.02). Residual antigenic but not functional evidence of the interventional agents remained in pleural fluids at 72 hours after tetracycline. No local or systemic bleeding occurred because of either interventional agent. The data demonstrate that single-chain urokinase inhibits, whereas lysin-receptor complexes attenuate, adhesion formation in tetracycline-induced pleural injury in rabbits.