The role of matrix metalloproteinases -9 and -2 in development of neonatal chronic lung disease.

Abstract

Matrix metalloproteinases (MMPs) -9 and -2 degrade type-IV collagen, a major constituent of lung basement membrane, and may have a role in the pathogenesis of neonatal chronic lung disease (CLD). We determined factors influencing MMP levels in neonatal bronchoalveolar lavage (BAL) fluid to establish whether an imbalance between MMP and its inhibitor could be implicated in CLD. We measured MMP-9 and -2 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in 316 BAL fluid samples from 121 babies of gestational ages 23 to 42 wk over the first 14 d of life to determine effects of gestation and postnatal age. Median MMP-9, -2, TIMP-1 and MMP-9/TIMP-1 ratio in BAL were further studied in a subgroup of 85 babies <33 wk gestation to determine their ability to predict CLD and to establish effects of antenatal corticosteroid therapy (ANCS). MMP-9, -2 and TIMP levels did not vary with postnatal age over the first week. Median MMP-9 levels and MMP-9/TIMP-1 ratio increased with decreasing gestation in preterm babies. The MMP-9/TIMP-1 ratio was higher in babies who developed CLD, implying a proteinase/antiproteinase imbalance, but this association disappeared when controlled for gestational age. ANCS had no effect on BAL fluid MMP or TIMP levels. MMPs may have a role in the development of lung injury and fibrosis, but estimating their levels in the first week of life does not help with prediction of CLD.