Single-chain urokinase alone or complexed to its receptor in tetracycline-induced pleuritis in rabbits

被引:39
作者
Idell, S
Mazar, A
Cines, D
Kuo, A
Parry, G
Gawlak, S
Juarez, J
Koenig, K
Azghani, A
Hadden, W
McLarty, J
Miller, E
机构
[1] Univ Texas Hlth Ctr, Dept Specialty Care Serv, Tyler, TX 75708 USA
[2] Attenuon, La Jolla, CA USA
[3] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[4] Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA
[5] N Shore Llj Res Inst, Dept Surg, Manhasset, NY USA
关键词
urokinase; fibrinolysis; pleural scarring;
D O I
10.1164/rccm.200204-313OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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.
引用
收藏
页码:920 / 926
页数:7
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