Transgenic PAI-1 expression improves host defense against Klebsiella pneumonia. (A) Wt mice were intranasally inoculated with 5 × 108 PFU Ad.PAI-1, and human PAI-1 levels were measured in lung homogenates after 0 and 24, 48, and 72 hours. Human PAI-1 in situ hybridization (B-C) showed a strong expression of PAI-1 mRNA in murine lung tissues 24 hours after Ad.PAI-1 intranasal (C) but not after Ad.RR5 (B) inoculation. Positive signal is indicated in black. Magnification, × 100. (D-F) Klebsiella pneumonia was induced in Wt mice at 24 hours after intranasal inoculation with 5 × 108 PFU Ad.PAI-1 or Ad.RR5; d-dimer was measured in lung homogenates at 0, 24, and 48 hours after infection (D), survival was monitored (E), and bacterial load was determined at 24 and 48 hours after infection (F). Data are means ± SE of 8 mice per genotype at each time point (A,D,F). Survival was evaluated using 16 mice per genotype. *P < .05 versus Ad.RR5-treated mice at the same time point.
