Regulation of plasminogen activator inhibitor-1 and urokinase by hyaluronan fragments in mouse macrophages

Maureen R. Horton, Mitchell A. Olman, Clare Bao, Kimberly E. White, Augustine M.K. Choi, Beek Yok Chin, Paul W. Noble, Charles J. Lowenstein

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Pulmonary inflammation and fibrosis are characterized by increased turnover and production of the extracellular matrix as well as an impairment of lung fibrinolytic activity. Although fragments of the extracellular matrix component hyaluronan induce macrophage production of inflammatory mediators, the effect of hyaluronan on the fibrinolytic mediators plasminogen activator inhibitor (PAI)-1 and urokinasetype plasminogen activator (uPA) is unknown. This study demonstrates that hyaluronan fragments augment steadystate mRNA, protein, and inhibitory activity of PAI-1 as well as diminish the baseline levels of uPA mRNA and inhibit uPA activity in an alveolar macrophage cell line. Hyaluronan fragments alter macrophage expression of PAI-1 and uPA at the level of gene transcription. Similarly, hyaluronan fragments augment PAI-1 and diminish uPA mRNA levels in freshly isolated inflammatory alveolar macrophages from bleomycin-treated rats. These data suggest that hyaluronan fragments influence alveolar macrophage expression of PAI-1 and uPA and may be a mechanism for regulating fibrinolytic activity during lung inflammation.

Original languageEnglish (US)
Pages (from-to)L707-L715
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number4 23-4
StatePublished - 2000


  • Chronic fibrosis
  • Extracellular matrix
  • Lung

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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