Exogenous rh-urokinase modifies inflammation and Pseudomonas aeruginosa infection in a rat chronic pulmonary infection model

D. A. Hart*, F. Green, P. Whidden, J. Henkin, D. E. Woods

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    7 Scopus citations

    Abstract

    The effect of recombinant human urokinase (rh-UK) in a rat model of chronic Pseudomonas aeruginosa pulmonary infection was studied. Efficacy was assessed by lung histology and quantitative bacteriology. Male Sprague-Dawley rats received 1 x 104 or 1 x 105 P. aeruginosa encapsulated in agar beads via the intratracheal route on day 1. Intratracheal administration of up to 12500 units of rh-UK on day 21 led to a dose-dependent disappearance of viable organisms from the lungs by day 24 in rats receiving 104 organisms. In slightly longer term infections (30 days), rh-UK was still effective in facilitating the disappearance of the organisms from the lungs of most of the treated animals. rh-UK was effective in eliminating organisms when animals were infected with 104, but not 105 bacteria. In vitro analysis revealed that rh-UK was not directly toxic for the organisms. Histologically, lungs from short-term infected control animals exhibited acute inflammation, inflammatory cell infiltrates, and fibrin deposition. Histology of lungs from UK-treated, short-term infected rats revealed decreased airway inflammation and cellular infiltration compared with infected controls. Lungs from infected animals treated with 12500 units of rh-UK were histologically indistinguishable from the lungs of uninfected control animals, except for the foreign body reaction. These results indicate that exogenous rh-UK may be efficacious in the treatment of pulmonary inflammation accompanying exposure to Gram-negative bacteria such as P. aeruginosa.

    Original languageEnglish (US)
    Pages (from-to)1127-1134
    Number of pages8
    JournalCanadian Journal of Microbiology
    Volume39
    Issue number12
    DOIs
    StatePublished - 1993

    Keywords

    • Pseudomonas aeruginosa infection
    • chronic pulmonary infection
    • fibrinolysis
    • urokinase

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Applied Microbiology and Biotechnology
    • Molecular Biology
    • Genetics

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