PEDIATRICS Vol. 108 No. 3 September 2001, pp. 686-692
Matrix Metalloproteinases-2, -8, and -9 and TIMP-2 in Tracheal Aspirates From Preterm Infants With Respiratory Distress
Received Nov 1, 2000; accepted Feb 8, 2001.
,,
From the * Hospital for Children and Adolescents, Helsinki
University Central Hospital; 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.
Department of Research Institute of
Dentistry, Biomedicum, University of Helsinki; § Department of Clinical
Veterinary Sciences, Faculty of Veterinary Medicine, University of
Helsinki; and Department of Obstetrics and Gynecology, Helsinki
University Central Hospital, Helsinki, Finland.
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