Early increased levels of matrix metalloproteinase-9 in neonates recovering from respiratory distress syndrome

Biol Neonate. 2006;89(1):6-14. doi: 10.1159/000088193. Epub 2005 Sep 8.

Abstract

Aim: Matrix metalloproteinases (MMPs) play an eminent role in airway injury and remodelling. We explored the hypothesis that pulmonary MMP levels would differ early after birth (2-4 days) between infants with resolving respiratory distress syndrome (RDS) and infants developing chronic lung disease of prematurity (CLD).

Methods: Thirty-two prematurely born infants (gestational age < or =30 weeks) diagnosed with RDS were included. In 13 infants RDS resolved while 19 developed CLD. MMP-2 and MMP-9 in bronchoalveolar lavage (BAL) fluids collected on postnatal days 2, 4, 7 and 10 were analyzed by zymography and densitometry. Immunochemistry was performed on BAL cells and lung tissue to identify cellular sources of MMP-9 in RDS and CLD.

Results: Median MMP-9 levels increased significantly on day 2 in BAL fluid from patients with resolving RDS (median values MMP-9 = 42.0 arbitrary units (AU)) compared to CLD patients (MMP-9 = 5.4 AU). MMP-9 and neutrophil lipocalin-associated MMP-9 (NGAL) were significantly higher on day 4 in BAL fluid from resolving RDS (MMP-9 = 65.8 AU; NGAL = 16.1 AU) compared to CLD (MMP-9 = 25.4 AU; NGAL = 2.0 AU), Levels of MMP-9 and NGAL increased subsequently on days 7 and 10 in CLD. No differences in MMP-2 levels were detected between RDS and CLD. Neutrophils, macrophages and alveolar type-II epithelial cells were identified as potential sources of MMP-9.

Conclusion: Our findings indicate differences in early MMP-9 BAL fluid levels between resolving RDS and developing CLD, which may relate to the ability to raise an early and adequate response to the initial injury.

MeSH terms

  • Acute-Phase Proteins / analysis
  • Aging
  • Bronchoalveolar Lavage Fluid
  • Chronic Disease
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Gestational Age
  • Humans
  • Immunohistochemistry
  • Infant, Newborn
  • Infant, Premature, Diseases / enzymology
  • Intensive Care, Neonatal
  • Lipocalin-2
  • Lipocalins
  • Lung / enzymology
  • Lung Diseases / enzymology
  • Lung Diseases / etiology
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 9 / analysis*
  • Proto-Oncogene Proteins / analysis
  • Respiratory Distress Syndrome, Newborn / enzymology*

Substances

  • Acute-Phase Proteins
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9