Fibrinolysis in LPS-induced chronic airway disease

Jordan D. Savov, David M. Brass, Katherine G. Berman, Erin McElvania, David A. Schwartz

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

To examine the role of the fibrinolytic system in LPS-induced airway disease, we compared the effect of a chronic LPS challenge in plasminogen activator inhibitor-deficient (C57BL/6JPAI-1-/-) mice and wild-type (WT) C57BL/6J mice. Physiological and biological assessments were performed, immediately after, and 4 wk after an 8-wk exposure to LPS or saline. Immediately after the LPS exposure, WT mice had increased estimates of airway reactivity to methacholine compared with C57BL/6JPAI-1-/- mice; however, airway inflammation was similar in both LPS-exposed groups. Significant increases in both active transforming growth factor (TGF)-β1 and active matrix metalloproteinase (MMP)-9 was detected after LPS exposure in WT but not C57BL/6JPAI-1-/- mice. C57BL/6JPAI-1-/- mice showed significantly less TGF-β1 in the lavage and higher MMP-9 in the lung tissue than WT mice at the end of exposure and 4 wk later. After LPS exposure, both WT and C57BL/6JPAI-1-/- mice had substantial expansion of the subepithelial area of the medium [diameter (d) = 90-129 μm]- and large (d > 129 μm)-size airways when compared with saline-exposed mice. Subepithelial fibrin deposition was prevalent in WT mice but diminished in C57BL/6JPAI-1-/-. PAI-1 expression by nonciliated bronchial epithelial cells was enhanced in LPS-exposed WT mice compared with the saline-exposed group. Four weeks after LPS inhalation, airway hyperreactivity and the expansion of the subepithelial area in the medium and large airways persisted in WT but not C57BL/6JPAI-1-/- mice. We conclude that an active fibrinolytic system can substantially alter the development and resolution of the postinflammatory airway remodeling observed after chronic LPS inhalation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume285
Issue number4 29-4
StatePublished - Oct 1 2003

Fingerprint

Fibrinolysis
Chronic Disease
Matrix Metalloproteinase 9
Transforming Growth Factors
Inhalation
Airway Remodeling
Plasminogen Inactivators
Methacholine Chloride
Therapeutic Irrigation
Plasminogen Activator Inhibitor 1
Fibrin
Inbred C57BL Mouse
Epithelial Cells
Inflammation
Lung

Keywords

  • Airway remodeling
  • Lung inflammation
  • Matrix metalloproteinase-9
  • Plasminogen activator inhibitor
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Fibrinolysis in LPS-induced chronic airway disease. / Savov, Jordan D.; Brass, David M.; Berman, Katherine G.; McElvania, Erin; Schwartz, David A.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 285, No. 4 29-4, 01.10.2003.

Research output: Contribution to journalArticle

Savov, Jordan D. ; Brass, David M. ; Berman, Katherine G. ; McElvania, Erin ; Schwartz, David A. / Fibrinolysis in LPS-induced chronic airway disease. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2003 ; Vol. 285, No. 4 29-4.
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