Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep.
BACKGROUND
Fetal lung maturation occurs after both maternal corticosteroid administration and chorioamnionitis. The effectors of this antenatally-induced lung maturation are not understood. Matrix metalloproteinases (MMPs) 2 and 9 are type-IV collagenases that can degrade alveolar basement membranes.


OBJECTIVE
We hypothesized that the structural changes of lung maturation by both antenatal corticosteroid treatment and chorioamnionitis would be associated with increases in these MMPs.


METHODS
64 pregnant ewes were randomly assigned to one of four treatment groups: intra-amniotic injection of 10 mg endotoxin, maternal intramuscular injection of 0.5 mg/kg betamethasone, both treatments combined or saline-treated controls. We quantified MMP-2 which is derived from connective tissue and MMP-9 which is predominantly derived from neutrophils in fetal lung fluid of lambs after maternal corticosteroid therapy and induction of chorioamnionitis and the combination of both therapies given at 109-111 days' gestational age with delivery 1, 5 or 15 days later.


RESULTS
Betamethasone, endotoxin and the combined treatments increased both surfactant pool size, lung gas volume and reduced alveolar wall thickness at 15 days. MMP-2 concentration was increased after betamethasone. MMP-9 concentration increased after endotoxin-induced chorioamnionitis but decreased by the combined treatments.


CONCLUSIONS
Lung maturation via different pathways may use different forms of collagenases for remodelling lung structure.
Sweet
David G
DG
Department of Child Health, The Queen's University of Belfast, UK.
Huggett
Matthew T
MT
Warner
Jane A
JA
Moss
Timothy J M
TJ
Kloosterboer
Nico
N
Halliday
Henry L
HL
Newnham
John P
JP
Kallapur
Suhas G
SG
Jobe
Alan H
AH
Kramer
Boris W
BW
D000650:Amnion / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001623:Betamethasone / Q000494:pharmacology*; D002821:Chorioamnionitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004731:Endotoxins / Q000494:pharmacology; D004790:Enzyme Induction; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000187:drug effects* / Q000201:enzymology; D005938:Glucocorticoids / Q000494:pharmacology*; D007273:Injections, Intramuscular; D018811:Maternal Exposure; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000002:abnormalities / Q000187:drug effects / Q000201:enzymology; D011663:Pulmonary Surfactants / Q000378:metabolism; D012756:Sheep
D004731:Endotoxins; D005938:Glucocorticoids; D011663:Pulmonary Surfactants; D001623:Betamethasone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9