Matrix metalloproteinases-2,-8, and-9 and TIMP-2 in tracheal aspirates from preterm infants with respiratory distress

Objectives. Matrix metalloproteinases (MMPs) are a family endoproteinases t hat act in degradation of extracellular matrix and basement membranes. The development of bronchopulmonary dysplasia (BPD) is characterized by early p ulmonary inflammation, increased microvascular permeability, and subsequent ly by disordered repair. The aims of our study were to characterize the pre sence and molecular weight forms of MMP-2, -8, and -9 and their specific in hibitor, tissue inhibitor of metalloproteinases (TIMP)-2, in lungs of prete rm infants during the early postnatal period and to determine whether level s 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 (gest ational age 27.0 +/-2.0 weeks; birth weight 875 +/- 246 g) during their fir st 5 postnatal days. The presence and molecular weight forms of MMPs and TI MP-2 were identified by Western immunoblotting, and their levels were evalu ated by densitometric scanning. Results. MMP-8 in TAF was higher in infants who needed treatment with surfa ctant (25.4 +/-6.3 vs 10.6 +/-1.5 arbitrary unit/secretory component of imm unoglobulin 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<plus/minus>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 T IMP-2 participates in the acute inflammatory process in respiratory distres s syndrome and may contribute to the development of chronic lung injury.