Extravascular fibrin, plasminogen activator, plasminogen activator inhibitors, and airway hyperresponsiveness
J. Clin. Invest. Scott S. Wagers, et al. 114:104 doi:10.1172/JCI19569 [
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Figure 6The effect of nebulized fibrinolytic agent, tPA, on the response to methacholine in mice with allergic airway inflammation. The response to a single dose of 12.5 mg/ml of nebulized methacholine administered 15 minutes after administration of saline (black bars) or tPA (white bars) is shown on the ordinate as the percentage of increase from baseline. An increased value indicates an increased response to methacholine. Mice with allergic airway inflammation (
n = 7) that had been exposed to tPA had a significantly reduced response to methacholine compared with those exposed to saline alone (
n = 7):
Rn, 99.2% ± 16% compared with 267% ± 62% (
P < 0.03);
Gti, 102% ± 23% compared with 225% ± 30% (
P < 0.01); and
Hti, 71% ± 30% compared with 284% ± 92% (
P < 0.05). In terms of
Rn and
Gti, the response to methacholine in mice with airway inflammation that had been exposed to nebulized tPA (
n = 7) was similar to the response in mice without airway inflammation exposed to saline (
n = 10):
Rn, 99.2% ± 16% compared with 119% ± 14%;
Gti, 102% ± 23% compared with 137% ± 21%. Nebulized tPA did not completely reduce the response in terms of
Hti to the level seen in controls: 71.2% ± 30% compared with 25.6% ± 2.7%.
