Plasminogen activator inhibitor-1 in acute hyperoxic mouse lung injury.

Barazzone-Argiroffo, Constance; Belin, Dominique; Piguet, P F; Vassalli, Jean‐Dominique; Sappino, André‐Pascal

doi:10.1172/jci119089

Cited by 128 publications

(106 citation statements)

References 36 publications

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“…Although previous studies have shown a decrease in inflammation in PAI-1 Ϫ/Ϫ mice in a murine model of Ag-induced arthritis (54) and after hyperoxic-induced lung injury (29), to our knowledge this is the first study showing a decrease in neutrophil recruitment to the lung in a model of acute lung inflammation in mice deficient for PAI-1. Our findings, however, are in contrast to those of Rijneveld et al (30), which found no decrease in alveolar neutrophil recruitment in PAI-1 Ϫ/Ϫ mice administered S. pneumoniae.…”

Section: Discussionmentioning

confidence: 62%

“…Septal thickening, lung inflammation, and overall mortality were improved in PAI-1-deficient mice in a hyperoxia model of lung injury, although a direct assessment of neutrophil recruitment to the alveolar compartment was not performed in that study (29). In contrast, neutrophil recruitment to the lung was not diminished in PAI-1-deficient mice after intratracheal (IT) inoculation of Streptococcus pneumoniae (30), or in a model of chronic LPS exposure (31).…”

Section: P Lasminogen Activator Inhibitor-1 (Pai-1)mentioning

confidence: 91%

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Regulation of Lipopolysaccharide-Induced Lung Inflammation by Plasminogen Activator Inhibitor-1 through a JNK-Mediated Pathway

Arndt

Young

Worthen

2005

The Journal of Immunology

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The neutrophil is of undoubted importance in lung inflammation after exposure to LPS. We have shown recently that systemic inhibition of JNK decreased neutrophil recruitment to the lung after exposure to LPS, although the mechanisms underlying this inhibition are incompletely understood. As plasminogen activator inhibitor-1 (PAI-1) accentuates cell migration, with JNK activation recently shown to up-regulate PAI-1 expression, this suggested that systemic JNK inhibition may down-regulate LPS-induced pulmonary neutrophil recruitment through a decrease in PAI-1 expression. We show in this study that exposure of mice to aerosolized LPS increased PAI-1 expression in the lung and alveolar compartment, which was decreased by pretreatment with the JNK inhibitor SP600125. Exogenous, intratracheally administered PAI-1 prevented the inhibition of pulmonary neutrophil recruitment in the setting of systemic JNK inhibition, thereby suggesting a role for PAI-1 in the JNK-mediated pathway regulating LPS-induced neutrophil recruitment. In addition, PAI-1−/− mice had a decrease in neutrophil recruitment to the alveolar compartment after exposure to LPS, compared with wild-type controls, further suggesting a role for PAI-1 in LPS-induced lung inflammation. An increase in the intravascular level of KC is a likely mechanism for the inhibition of pulmonary neutrophil recruitment after LPS exposure in the setting of decreased PAI-1 expression, as systemic KC levels after exposure to LPS were increased in PAI-1-deficient mice and in mice pretreated with SP600125, with augmentation of intravascular KC levels inhibiting neutrophil recruitment to the lung after exposure to LPS.

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Section: Discussionmentioning

confidence: 62%

Section: P Lasminogen Activator Inhibitor-1 (Pai-1)mentioning

confidence: 91%

Regulation of Lipopolysaccharide-Induced Lung Inflammation by Plasminogen Activator Inhibitor-1 through a JNK-Mediated Pathway

Arndt

Young

Worthen

2005

The Journal of Immunology

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“…PAI-1-deficient mice are resistant to pulmonary fibrosis after lung injury, presumably due to accelerated fibrinolysis (35). PAI-1-overexpressing mice suffered a severe lung injury and deposition of ECM after bleomycin challenge (35) or hyperoxia (36), whereas PAI-1-deficient mice were protected against such fibrotic reaction. The finding that the level of PAI-1 gene expression is strongly correlated with the amount of collagen accumulation within lung tissues suggests that the balance of fibrinolytic activity within the lung is an important determinant of the pulmonary response to inflammatory injury.…”

Section: Ast Cells Are Multifunctional Effector Cells That Partic-mentioning

confidence: 99%

Production of Plasminogen Activator Inhibitor-1 by Human Mast Cells and Its Possible Role in Asthma

Cho¹,

Tam²,

Demissie-Sanders³

et al. 2000

The Journal of Immunology

118

114

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The plasminogen activator inhibitor type 1 (PAI-1) has an essential role in tissue remodeling. The PAI-1 gene was induced by a combination of phorbol ester and calcium ionophore at the highest level among the inducible human mast cell genes that we have analyzed on a DNA microarray. PAI-1 was secreted by both a human mast cell line (HMC)-1 and primary cultured human mast cells upon stimulation, whereas PAI-1 was undetectable in either group of unstimulated cells. The secretion of PAI-1 was due to de novo synthesis of PAI-1 rather than secretion of preformed PAI-1. The functional significance of PAI-1 secretion was demonstrated by complete inhibition of tissue-type plasminogen activator activity with supernatants of stimulated HMC-1 cells. Furthermore, we were able to regulate PAI-1 gene expression in HMC-1 cells by known therapeutic agents. High-dose (1 μM) dexamethasone induced PAI-1 mRNA expression. Cyclosporin down-regulated the expression of the PAI-1 gene. Cycloheximide abrogated PAI-1 mRNA expression, suggesting that transcription of the PAI-1 gene requires de novo synthesis of early gene products, including transcription factors. Finally, we demonstrated PAI-1 in lung mast cells from a patient with asthmatic attack by double-immunofluorescence study. This is the first report demonstrating that activated human mast cells release a striking amount of functionally active PAI-1. These results suggest that PAI-1 could play an important role in airway remodeling of asthma, and inhibition of PAI-1 activity could represent a novel therapeutic approach in the management of airway remodeling.

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“…Lung tissue was homogenized between a 60 ϫ 15 mm petri culture dish (Pyrex, Lowell, MA) and a 4-mL glass vial (Kimble Glass Inc., Raleigh, NC) in a sterile fashion (10).…”

Section: Organismmentioning

confidence: 99%

Antibiotic Prophylaxis Improves Ureaplasma-Associated Lung Disease in Suckling Mice

et al. 2009

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Ureaplasma infection is associated with increased lung disease in high-risk neonates. Our goal was to determine the impact of antibiotic prophylaxis on Ureaplasma and oxygen-induced lung disease in newborn mice. In animal model development and prophylaxis experiments, pups were randomly assigned to either 0.8 or 0.21 inspired oxygen concentration [fraction of inspired oxygen (FiO 2 )] from 1 to 14 d of age and either Ureaplasma or 10 B media daily from 1 to 3 d. All pups were observed for growth and survival. Surviving pups had culture and PCR evaluated for blood, bronchoalveolar lavage, and lung, and lung weights, pathology, morphometry, histology, and immunohistochemistry were determined. In prophylaxis experiments, erythromycin, azithromycin, or normal saline was given for the first 3 d, and minimum inhibitory concentration and pharmacokinetics were determined. In model development, 0.8 FiO 2 and Ureaplasma infection survival and growth were significantly decreased and lung edema and inflammation were significantly increased. In prophylaxis experiments, we observed significantly improved survival and growth with azithromycin versus normal saline controls, whereas erythromycin was not significantly different from controls, and decreased inflammatory response with azithromycin versus normal saline and erythromycin. In a neonatal mouse model of Ureaplasma and oxygen-induced lung disease, appropriate antibiotic prophylaxis improves survival and morbidity and decreases lung inflammation. (Pediatr Res 66: 197-202, 2009)

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Plasminogen activator inhibitor-1 in acute hyperoxic mouse lung injury.

Cited by 128 publications

References 36 publications

Regulation of Lipopolysaccharide-Induced Lung Inflammation by Plasminogen Activator Inhibitor-1 through a JNK-Mediated Pathway

Regulation of Lipopolysaccharide-Induced Lung Inflammation by Plasminogen Activator Inhibitor-1 through a JNK-Mediated Pathway

Production of Plasminogen Activator Inhibitor-1 by Human Mast Cells and Its Possible Role in Asthma

Antibiotic Prophylaxis Improves Ureaplasma-Associated Lung Disease in Suckling Mice

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