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

Steven Idell*, Andrew Mazar, Douglas Cines, Alice Kuo, Graham Parry, Susan Gawlak, Jose Juarez, Kathy Koenig, Ali Azghani, Will Hadden, Jerry McLarty, Edmund Miller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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 ≤ 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.

Original languageEnglish (US)
Pages (from-to)920-926
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume166
Issue number7
DOIs
StatePublished - Oct 1 2002

Keywords

  • Fibrinolysis
  • Pleural scarring
  • Urokinase

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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