Background: So far studies showing the role of the plasmin system in airway remodelling have been conducted using in vitro models. The aim of the present study was to determine plasmin system regulation in an in vivo rat model of asthma.
Methods: Asthma in Wistar rats was induced by ovalbumin (OVA) sensitization followed by an OVA challenge (OVA/OVA, n = 6). Control groups were saline-sensitized challenged with OVA (VEH/OVA, n = 6) and OVA-sensitized challenged with saline (OVA/VEH, n = 6). Plasmin system components were determined in the plasma by ELISA. Plasminogen activator inhibitor-1 (PAI-1) was localized by an immunohistochemical reaction.
Results: Sensitization and challenge with OVA caused thickening of the airway wall, hypertrophy of smooth muscle cells, infiltration of inflammatory cells, subepithelial fibrosis, epithelial and endothelial lesions. Serum total IgE was significantly higher in OVA-sensitized rats as compared to VEH-sensitized control groups. Tissue plasminogen activator activity was significantly decreased in asthmatic animals (4.48 +/- 0.4 vs. 6.7 +/- 0.3 ng/ml for OVA/OVA and OVA/VEH; p < 0.05), and PAI-1 activity was statistically significantly higher in asthma rats (0.8 +/- 0.05 vs. 0.5 +/- 0.03 ng/ml for OVA/OVA vs. OVA/VEH; p < 0.05). alpha2-Antiplasmin was higher in rats receiving OVA sensitization than in those that were sham sensitized (p < 0.05). Immunohistochemical staining for PAI-1in the lungs of asthmatic animals showed very strong PAI-1 expression in lung inflammatory cells.
Conclusions: We have demonstrated for the first time the existence of PAI-1 in lung inflammatory cells of rats with asthma. This finding was consistent with the superiority of plasmin system inhibition over activation in plasma.
Copyright (c) 2008 S. Karger AG, Basel.