title: Early increased levels of matrix metalloproteinase-9 in neonates recovering from respiratory distress syndrome.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. w.dik@erasmusmc.nl
authors.forename: Willem A
authors.initials: WA
authors.lastname: Dik
authors.forename: Anton H L C
authors.initials: AH
authors.lastname: van Kaam
authors.forename: Tamara
authors.initials: T
authors.lastname: Dekker
authors.forename: Brigitta A E
authors.initials: BA
authors.lastname: Naber
authors.forename: Daphne J
authors.initials: DJ
authors.lastname: Janssen
authors.forename: A A
authors.initials: AA
authors.lastname: Kroon
authors.forename: Luc J I
authors.initials: LJ
authors.lastname: Zimmermann
authors.forename: Marjan A
authors.initials: MA
authors.lastname: Versnel
authors.forename: René
authors.initials: R
authors.lastname: Lutter
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000375:Aging; D001992:Bronchoalveolar Lavage Fluid; D002908:Chronic Disease; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000201:enzymology; D015931:Intensive Care, Neonatal; D000071068:Lipocalin-2; D054834:Lipocalins; D008168:Lung / Q000201:enzymology; D008171:Lung Diseases / Q000201:enzymology / Q000209:etiology; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012127:Respiratory Distress Syndrome, Newborn / Q000201:enzymology*
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9