Matrix Metalloproteinases-2, -8, and -9 and TIMP-2 in Tracheal Aspirates From Preterm Infants With Respiratory Distress

Abstract

Objectives. Matrix metalloproteinases (MMPs) are a family endoproteinases that act in degradation of extracellular matrix and basement membranes. The development of bronchopulmonary dysplasia (BPD) is characterized by early pulmonary inflammation, increased microvascular permeability, and subsequently by disordered repair. The aims of our study were to characterize the presence and molecular weight forms of MMP-2, -8, and -9 and their specific inhibitor, tissue inhibitor of metalloproteinases (TIMP)-2, in lungs of preterm infants during the early postnatal period and to determine whether levels of these MMPs and TIMP-2 in tracheal aspirate fluid (TAF) are associated with acute or chronic lung morbidity of the preterm infant. Methods. TAF samples were collected from 16 intubated preterm infants (gestational age 27.0 ± 2.0 weeks; birth weight 875 ± 246 g) during their first 5 postnatal days. The presence and molecular weight forms of MMPs and TIMP-2 were identified by Western immunoblotting, and their levels were evaluated by densitometric scanning. Results. MMP-8 in TAF was higher in infants who needed treatment with surfactant (25.4 ± 6.3 vs 10.6 ± 1.5 arbitrary unit/secretory component of immunoglobulin A [AU/SC]) and in whom BPD developed (N = 6; 27.6 ± 5.2 vs 15.1 ± 5.0 AU/SC). TIMP-2 levels were lower in infants with initial arterial to alveolar oxygen tension ratios <0.22 (2.7 ± 1.1 vs 16.8 ± 7.4 AU/SC) and in infants needing mechanical ventilation for >1 week (5.2 ± 2.1 vs 22.8 ± 11.7 AU/SC). Conclusions. In preterm infants, an imbalance between pulmonary MMP-8 and TIMP-2 participates in the acute inflammatory process in respiratory distress syndrome and may contribute to the development of chronic lung injury.