Plasminogen Activator Activity in Preterm Infants with Respiratory Distress Syndrome: Relationship to the Development of Bronchopulmonary Dysplasia

Singhal, Kamal Kumar; Parton, Lance

doi:10.1203/00006450-199602000-00007

Cited by 24 publications

(19 citation statements)

References 27 publications

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“…Conversely, uPA, being present essentially within the alveolar compartment, may not be crucial until alveolar leakage and subsequent fibrin deposition is present, after 72 h of hyperoxia. Several authors have reported that decreased fibrinolytic activity associated with experimental and clinical pulmonary lesions is a good predictive marker for the subsequent development of fibrosis (28,34,35). In accordance with this, it has been shown recently that PAI-1-mediated inhibition of fibrinolysis influences the severity of bleomycin-induced chronic lung fibrosis (36).…”

Section: Discussionsupporting

confidence: 51%

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

Barazzone-Argiroffo

Belin²,

Piguet³

et al. 1996

J. Clin. Invest.

127

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Hyperoxia-induced lung disease is associated with prominent intraalveolar fibrin deposition. Fibrin turnover is tightly regulated by the concerted action of proteases and antiproteases, and inhibition of plasmin-mediated proteolysis could account for fibrin accumulation in lung alveoli. We show here that lungs of mice exposed to hyperoxia overproduce plasminogen activator inhibitor-1 (PAI-1), and that PAI-1 upregulation impairs fibrinolytic activity in the alveolar compartment. To explore whether increased PAI-1 production is a causal or only a correlative event for impaired intraalveolar fibrinolysis and the development of hyaline membrane disease, we studied mice genetically deficient in PAI-1. We found that these mice fail to develop intraalveolar fibrin deposits in response to hyperoxia and that they are more resistant to the lethal effects of hyperoxic stress. These observations provide clear and novel evidence for the pathogenic contribution of PAI-1 in the development of hyaline membrane disease. They identify PAI-1 as a major deleterious mediator of hyperoxic lung injury. ( J. Clin. Invest. 1996. 98:2666-2673.)

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Section: Discussionsupporting

confidence: 51%

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

Barazzone-Argiroffo

Belin²,

Piguet³

et al. 1996

J. Clin. Invest.

127

View full text Add to dashboard Cite

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“…We know fibrin deposits are found within the lung's intravascular, interstitial and intra-alveolar spaces in RDS (12). It is also known that platelets play an important role in inflammation.…”

Section: Activated Inflammation and Clotting In Rdsmentioning

confidence: 99%

“…As is known from histopathologic studies, fibrin is a major part of hyaline membranes and therefore hyaline membranes can be regarded as locally produced clots in RDS (12,13). Schmidt described that intravascular thrombin-antithrombin III complex formation was related to disease severity in RDS (14).…”

mentioning

confidence: 99%

Early Activation of Inflammation and Clotting in the Preterm Lamb with Neonatal RDS: Comparison of Conventional Ventilation and High Frequency Oscillatory Ventilation

Jaarsma¹,

Braaksma²,

Geven³

et al. 2001

Pediatr Res

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“…Aspirates were collected during routine tracheal suctioning of mechanically ventilated newborns (15). Infants were positioned in a supine posture with head midline.…”

Section: Tracheal Aspirate Collectionmentioning

confidence: 99%

Interleukin (IL)-1β in Tracheal Aspirates from Premature Infants Induces Airway Epithelial Cell IL-8 Expression via an NF-κB Dependent Pathway

et al. 2004

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Tracheal aspirate IL-8 concentration and airway epithelial cell IL-8 expression are each increased in premature infants undergoing mechanical ventilation. We sought to determine the cytokines responsible for IL-8 expression in this context. Tracheal aspirates were collected from 18 mechanically ventilated premature infants. IL-8 protein abundance was high in tracheal aspirates from ventilated premature infants (mean, 5806 Ϯ 4923 pg/mL). IL-1␣ (mean, 20 Ϯ 6 pg/mL), IL-1␤ (mean 67 Ϯ 46 pg/mL), and tumor necrosis factor (TNF)-␣ (mean, 8 Ϯ 2 pg/mL) were also found. Incubation of tracheal aspirates with 16HBE14o-human bronchial epithelial cells increased IL-8 protein in both cell lysates and supernatants, as well as transcription from the IL-8 promoter. Aspirates also induced nuclear factor (NF)-B activation. Mutation of the IL-8 promoter NF-B site abolished aspirate-induced IL-8 transcription. Endotoxin concentrations in the tracheal aspirates were negligible and incapable of inducing IL-8 promoter activity. Finally, incubation of tracheal aspirates with a neutralizing antibody against IL-1␤ reduced epithelial cell IL-8 production, whereas neutralizing antibodies against IL-1␣ and TNF-␣ had no effect. We conclude that airway fluid from mechanically ventilated premature infants contains soluble factors capable of inducing airway epithelial cell IL-8 expression via a NF-B-dependent pathway, and that IL-1␤ plays a specific role in this process. Despite advances in neonatal care, BPD continues to be a major cause of morbidity and mortality in premature neonates. Accordingly, interest remains high in the pathogenesis of this chronic lung disease. Recent evidence suggests the importance of inflammation in the pathogenesis of BPD. During the first days of postnatal life, an influx of polymorphonuclear leukocytes and macrophages is seen in the tracheal aspirates of mechanically ventilated premature infants who later develop BPD (1). Elevations of pro-inflammatory cytokines such as IL-8, IL-6, IL-1␤, and TNF-␣ are also seen (2-7). Similar findings are present in animal models of BPD (8) and hyperoxic exposure (9). Of the cytokines implicated in BPD, IL-8 may be of special importance, as it is the most potent neutrophil chemotactic factor.IL-8 may be elaborated by macrophages, T-lymphocytes, neutrophils, and respiratory epithelial cells (4). In a recent study examining IL-8 expression in the lung tissue of neonates with hyaline membrane disease, the majority of cases demonstrated IL-8 immunoreactivity in fetal and neonatal neutrophils, and in almost half of these cases, airway epithelial cell IL-8 expression (10). An earlier study in ventilated preterm infants detected IL-8 in bronchoalveolar macrophages, neutrophils, and exfoliated epithelial cells (6). In newborn rats, hyperoxic exposure induced the expression of cytokineinduced neutrophil chemoattractant-1, an IL-8 homologue, in alveolar macrophages and epithelial cells (9). Numerous studies have shown that cultured airway epithelial cells may produce IL-8 in response to a...

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Plasminogen Activator Activity in Preterm Infants with Respiratory Distress Syndrome: Relationship to the Development of Bronchopulmonary Dysplasia

Cited by 24 publications

References 27 publications

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

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

Early Activation of Inflammation and Clotting in the Preterm Lamb with Neonatal RDS: Comparison of Conventional Ventilation and High Frequency Oscillatory Ventilation

Interleukin (IL)-1β in Tracheal Aspirates from Premature Infants Induces Airway Epithelial Cell IL-8 Expression via an NF-κB Dependent Pathway

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