Journal article

Publication year: 2010

Pages: 1355-1366

Journal: American Journal of Respiratory and Critical Care Medicine

Volume number: 181

Issue number: 12

ISSN: 1073-449X

eISSN: 1535-4970

Open access status: Green

DOI Link: https://doi.org/10.1164/rccm.200901-0015OC

Publisher: American Thoracic Society

Abstract: 

Rationale Urokinase-type plasminogen activator (uPA) regulates extracellular proteolysis in lung injury and repair. Although alveolar expression of uPA increases, procoagulant activity predominates.

Objectives: This study was designed to investigate whether uPA alters the expression of tissue factor (TI), the major initiator of the coagulation cascade, in lung epithelial cells (ECs).

Methods: Bronchial, primary airway ECs and C57B6 wild-type, uPA-deficient (uPA(-/-)) mice were exposed to phosphate-buffered saline, uPA, or LPS. lmmunohistochemistry, protein, cellular, and molecular techniques were used to assess TF expression and activity.

Measurements and Main Results: uPA enhanced TF mRNA and protein expression, and TF-dependent coagulation in lung ECs. uPA-induced expression of TF involves both increased synthesis and enhanced stabilization of TF mRNA. uPA catalytic activity had little effect on induction of TF. By contrast, deletion of the uPA receptor binding growth factor domain from uPA markedly attenuated the induction of TI, suggesting that uPA receptor binding is sufficient for TI induction. Lung tissues of uPA-deficient mice expressed less TF protein and mRNA compared with wild-type mice. In addition, intratracheal instillation of mouse uPA increased TI mRNA and protein expression and accelerated coagulation in lung tissues. uPA-/- mice exposed to LPS failed to induce TF.

Conclusions: uPA increased TF expression and TF-dependent coagulation in the lungs of mice. We hypothesize that uPA-mediated induction of TI occurs in lung ECs to promote increased fibrin deposition in the airways during acute lung injury.

Harvard Citation style: Shetty, S., Bhandary, Y., Shetty, S., Velusamy, T., Shetty, P., Bdeir, K., et al. (2010) Induction of Tissue Factor by Urokinase in Lung Epithelial Cells and in the Lungs, American Journal of Respiratory and Critical Care Medicine, 181(12), pp. 1355-1366. https://doi.org/10.1164/rccm.200901-0015OC

APA Citation style: Shetty, S., Bhandary, Y., Shetty, S., Velusamy, T., Shetty, P., Bdeir, K., Gyetko, M., Cines, D., Idell, S., Neuenschwander, P., Ruppert, C., Guenther, A., Abraham, E., & Shetty, R. (2010). Induction of Tissue Factor by Urokinase in Lung Epithelial Cells and in the Lungs. American Journal of Respiratory and Critical Care Medicine. 181(12), 1355-1366. https://doi.org/10.1164/rccm.200901-0015OC