Published online April 3, 2006
PEDIATRICS Vol. 117 No. 4 April 2006, pp. 1226-1234 (doi:10.1542/peds.2005-0870)
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High Concentrations of Plasminogen Activator Inhibitor-1 in Lungs of Preterm Infants With Respiratory Distress Syndrome

Katariina Cederqvist, MDa, Vappu Sirén, PhDc, Jari Petäjä, MD, PhDa,d, Antti Vaheri, MD, PhDc, Caj Haglund, MD, PhDb and Sture Andersson, MD, PhDa

a Departments of Pediatrics
b Surgery
c Haartman Institute, University of Helsinki, Helsinki, Finland
d Department of Pediatrics, Helsinki University Central Hospital, Jorvi Hospital, Espoo, Finland

BACKGROUND. Among preterm infants, respiratory distress syndrome (RDS) is characterized by the presence of intraalveolar fibrin deposition. Fibrin monomers inhibit surfactant function effectively. However, little is known about potential disturbances of intraalveolar fibrinolysis in RDS. We studied levels of major plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) in lungs of preterm infants with RDS.

METHODS. The antigen levels of PAI-1, tPA, and uPA were measured in 262 samples of tracheal aspirate fluid collected from 37 intubated preterm infants during the first 2 postnatal weeks. To examine the expression of PAI-1, tPA, and uPA in lung tissue, immunohistochemical analyses were performed on autopsy specimens from 7 preterm infants with RDS and 6 newborn infants without pulmonary pathologic conditions.

RESULTS. For infants with an immature surfactant profile, as indicated by lecithin/sphingomyelin ratios in tracheal aspirate fluid of <10, PAI-1 levels and ratios of PAI-1 to uPA and tPA were significantly higher during postnatal days 1 to 2, compared with infants with lecithin/sphingomyelin ratios of ≥10. Moreover, infants who subsequently developed bronchopulmonary dysplasia (BPD) (n = 15) had higher PAI-1 levels on days 3 to 4 and days 7 to 8 than did those who survived without BPD. For preterm infants with RDS, immunohistochemical analyses demonstrated increased expression of PAI-1, tPA, and uPA predominantly in alveolar epithelium.

CONCLUSIONS. High concentrations of PAI-1 and an increased ratio of PAI-1 to uPA, with a concurrently less-increased ratio of PAI-1 to tPA, are associated with the severity of RDS among preterm infants during the first postnatal days. Pulmonary inhibition of fibrinolysis is a pathophysiologic feature of RDS and may play a role in the development of BPD.

Key Words: respiratory distress syndrome • preterm • respiratory distress syndrome

Abbreviations: RDS—respiratory distress syndrome • BPD—bronchopulmonary dysplasia • tPA—tissue-type plasminogen activator • uPA—urokinase-type plasminogen activator • PAI—plasminogen activator inhibitor • TAF—tracheal aspirate fluid • SC—secretory component of IgA • ELISA—enzyme-linked immunosorbent assay

Accepted Aug 31, 2005.


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