Airway inflammatory cell responses to intra-amniotic lipopolysaccharide in a sheep model of chorioamnionitis.
Chorioamnionitis, a risk factor for bronchopulmonary dysplasia in preterm infants, causes an influx of inflammatory cells into the fetal lung. Using a fetal sheep model, we evaluated the time course of activation, functional maturity, and apoptosis of the leukocytes recruited to the fetal air spaces by lipopolysaccharide (LPS). Time-mated sheep were given intra-amniotic injections with 10 mg of Escherichia coli LPS or saline 2 or 7 days before preterm delivery at 124 days of gestation (term is 150 days). Both neutrophils and monocytes in bronchoalveolar lavage fluid (BALF) had activated NF-kappaB after 2- and 7-day LPS exposures. These neutrophils and monocytes expressed the activation factor CD11b and the maturation factor PU.1 at 2 days, and increased PU.1 expression was detected in macrophages at 7 days. Leukocyte oxidative burst activity was greatest at 7 days. BALF lipid peroxidation increased fivefold at 2 days, while protein carbonyls increased eightfold at 7 days. Nitrative stress was not detected in the BALF, but leukocytes in the lung expressed nitric oxide synthase (NOS)II (inducible NOS). BALF leukocytes expressed the antioxidant peroxiredoxin V. Lung glutathione peroxidase was also increased with LPS exposure. There was minimal apoptosis of airway and lung leukocytes assessed by caspase-3 activation. Intra-amniotic LPS recruits leukocytes to the fetal air space that have a persistent activation. These results have implications for the pathogenesis of lung inflammatory disorders in the preterm.
Cheah
Fook-Choe
FC
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229-3039, USA.
Pillow
J Jane
JJ
Kramer
Boris W
BW
Polglase
Graeme R
GR
Nitsos
Ilias
I
Newnham
John P
JP
Jobe
Alan H
AH
Kallapur
Suhas G
SG
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002821:Chorioamnionitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008171:Lung Diseases / Q000151:congenital / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D011247:Pregnancy; D012756:Sheep
D000975:Antioxidants; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B