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Cytokine Modulation of Plasminogen Activator/Plasminogen Activator Inhibitor Expression by Pulmonary Epithelial Cells

1992; Elsevier BV; Volume: 101; Issue: 3 Linguagem: Inglês

10.1378/chest.101.3_supplement.21s

1931-3543

Bruce C. Marshall, N. V. Rao, Brent R. Brown, John R. Hoidal,

Chronic Obstructive Pulmonary Disease (COPD) Research

Epithelial cell injury is a prominent feature in a variety of airway disorders including asthma, bronchitis, and cystic fibrosis. However, little is known about the epithelial repair process that follows airway injury. There is substantial evidence to suggest that plasminogen activators (PA), particularly urokinase-type PA (u-PA), play an important role in cell migration and tissue remodeling that accompanies repair. 1 Saksela O Rifkin DB. Cell associated plasminogen activation: regulation and physiologic functions. Ann Rev Cell Biol. 1988; 4: 93-126 Crossref PubMed Scopus (717) Google Scholar Recent studies suggest that changes in PA/PA inhibitor (PAI) expression in the adult respiratory distress syndrome correlate with the widespread intraalveolar fibrin deposition characteristic of the early phase of the injury. 2 Idell S Peters J James KK Fair DS Coalson JJ. Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in adult respiratory distress syndrome. J Clin Invest. 1989; 84: 181-193 Crossref PubMed Scopus (66) Google Scholar ,3 Bertozzi P Astedt B Zenzius L Lynch K LeMaire F Zapol W et al. Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome. N Engl J Med. 1990; 322: 890-897 Crossref PubMed Scopus (243) Google Scholar It has been shown that normal human bronchial epithelial cells, 4 Gerwin BI Keski-Oja J Seddon M Lechner JF Harris CC. TGF-β1 modulation of urokinase and PAI-1 expression in human bronchial epithelial cells. Am J Physiol. 1990; 259: 262-269 PubMed Google Scholar rat alveolar epithelial cells, 5 Marshall BC Sageser DS Rao NV Emi M Hoidal JR. Alveolar epithelial cell plasminogen activator: characterization and regulation. J Biol Chem. 1990; 265: 8198-8204 PubMed Google Scholar ,6 Gross TJ Simon RH Kelly CJ Sirrin RG. Rat alveolar epithelial cells concomitantly express plasminogen activator inhibitor-1 and urokinase. Am J Physiol. 1991; 260: 286-295 PubMed Google Scholar and a human pulmonary epithelial cell line 7 Keski-Oja J Blasi F Leof EB Moses HL. Regulation of the synthesis and activity of urokinase plasminogen activator in A549 human lung carcinoma cells by transforming growth factor-β. J Cell Biol. 1988; 106: 451-459 Crossref PubMed Scopus (95) Google Scholar express u-PA and PAI-type 1 (PAI-1). Thus, pulmonary epithelial cells likely directly contribute to the extensive remodeling process that follows lung injury. The key modulating factors of epithelial cell u-PA/PAI-1 expression and their mechanism(s) of action have not been fully delineated.