Early increased levels of matrix metalloproteinase-9 in neonates recovering from respiratory distress syndrome.
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.
Dik
Willem A
WA
Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. w.dik@erasmusmc.nl
van Kaam
Anton H L C
AH
Dekker
Tamara
T
Naber
Brigitta A E
BA
Janssen
Daphne J
DJ
Kroon
A A
AA
Zimmermann
Luc J I
LJ
Versnel
Marjan A
MA
Lutter
René
R
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*
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