Long-Term Pulmonary Effects of Intrauterine Exposure to Endotoxin Following Preterm Birth in Sheep

Abstract

Our aim was to determine whether fetal exposure to intraamniotic lipopolysaccharide (LPS) persistently alters the lungs following moderate preterm birth. Fetal sheep were exposed to LPS (1 mg/d) or saline from 0.75 to preterm birth at 0.90 of gestation. Eleven weeks after preterm birth, lung structure was unaltered. Interleukin (IL)-1β messenger RNA (mRNA) levels were elevated in lungs of LPS-exposed lambs (P < .05) but IL-1β protein levels were unaltered. Lung mRNA levels of IL-6, IL-8 and tumor necrosis factor α, and percentage of inflammatory cells were not different between groups. Surfactant protein (SP)-A and SP-C mRNA levels and SP-B tissue protein expression were higher in LPS-exposed lambs than controls (all P < .05); however, expression of SP-A and SP-C proteins was reduced. Prenatal LPS exposure causes a persistent increase in gene expression of proinflammatory mediators and surfactant proteins and a decrease in lung tissue SP-A and -C protein expression after preterm birth, which may affect lung immunity.

Structural and functional correlations in a large animal model of bleomycin-induced pulmonary fibrosis

“…Measurements were made by superimposing custom-designed test grids over the lung parenchyma, which were generated using Image Pro. Tissue and airspace fractions were determined within parenchymal tissue by point-counting methods, as previously described [ 19 , 20 ]. Analyses were performed from a total of 15 fields at a final magnification of x200.…”

A novel segmental challenge model for bleomycin-induced pulmonary fibrosis in sheep

“…Alveolar epithelial cell (AEC) hyperplasia was assessed as present (1) or absent (0) [25,26]. Analyzes were performed for a total of 15 fields at a final magnification of x200.…”

Respiratory adaptation and surfactant composition of unanesthetized male and female lambs differ for up to 8 h after preterm birth

“…Relative surfactant protein (SP)-A, SP-B, SP-C and SP-D mRNA levels in lung tissue were measured using quantitative real-time PCR, as previously described (27). Quantitative real-time PCR was performed using a SYBR green detection method and a Stratagene Mx3000P detection system (Agilent Technologies, Santa Clara, CA).…”