Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin.
Chorioamnionitis is frequent in preterm labor and increases the risk of bronchopulmonary dysplasia. We hypothesized that intra-amniotic endotoxin injures the lung in utero, causing a sequence of inflammation and tissue injury similar to that which occurs in the injured adult lung. Preterm lamb lungs at 125 days gestational age were evaluated for indicators of inflammation, injury, and repair 5 h, 24 h, 72 h, and 7 days after 4 mg of intra-amniotic endotoxin injection. At 5 h, the epithelial cells in large airways expressed heat shock protein 70, and alveolar interleukin-8 was increased. Surfactant protein B (SP-B) decreased in alveolar type II cells at 5 h, and SP-B in lung tissue and alveolar lavage fluid increased by 72 h. By 24 h, neutrophils were recruited into the large airways, and cell death was the highest. Alveolar type II cells decreased by 25% at 24 h, and proliferation was highest at 72 h, consistent with tissue remodeling. Intra-amniotic endotoxin caused surfactant secretion, inflammation, cell death, and remodeling as indications of lung injury. The recovery phase was accompanied by maturational changes in the fetal lung.
Division of Pulmonary Biology, Cincinnati Children's Hospital, Cincinnati, Ohio 45229, USA.
Boris W
BW
Kramer
Susanne
S
Kramer
Machiko
M
Ikegami
Alan H
AH
Jobe
D000653:Amniotic Fluid; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004731:Endotoxins / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000196:embryology*; D011014:Pneumonia / Q000139:chemically induced* / Q000196:embryology* / Q000473:pathology / Q000503:physiopathology; D011510:Proteolipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000473:pathology; D011663:Pulmonary Surfactants / Q000378:metabolism; D012756:Sheep; D014945:Wound Healing
D004731:Endotoxins; D018840:HSP70 Heat-Shock Proteins; D016209:Interleukin-8; D011510:Proteolipids; D011663:Pulmonary Surfactants