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Plasminogen Activators and Inhibitors in the Corneas of Mice Infected with Pseudomonas aeruginosa

¹ From the Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan; and ² Molecular Innovations, Royal Oak, Michigan.

PURPOSE. To characterize the presence of plasminogen activators and their inhibitors in the corneas during the inflammatory response in naïve and immunized mice intracorneally infected with Pseudomonas aeruginosa.

METHODS. RT-PCR was used to detect gene expression for plasminogen activators and their inhibitors in naïve and immunized mice. Immunoblot analysis, zymography, and ELISA were used to demonstrate the syntheses of these proteins.

RESULTS. Naïve mice intracorneally infected with P. aeruginosa showed a temporally enhanced expression of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2), over a several-day holding period. Immunized mice demonstrated a lower and shorter expression of these factors over the same period. Expression of these factors at the mRNA and protein levels may have been due to enzymes and inhibitors present in inflammatory cells and in resident corneal cells.

CONCLUSIONS. These results show a correlation between the overexpression of the PA system in infected naïve mice as part of the inflammatory response, with eventual ocular destruction. Immunized mice exhibit a more balanced and shorter expression of the PA system, which may contribute to the restoration of corneal clarity.

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