Consequences of early postnatal lipopolysaccharide exposure on developing lungs in mice

Amrit Kumar Shrestha, Matthew L. Bettini, Renuka T. Menon, Vashisht Y.N. Gopal, Shixia Huang, Dean P. Edwards, Mohan Pammi, Roberto Barrios, Binoy Shivanna

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of infants that is characterized by interrupted lung development. Postnatal sepsis causes BPD, yet the contributory mechanisms are unclear. To address this gap, studies have used lipopolysaccharide (LPS) during the alveolar phase of lung development. However, the lungs of infants who develop BPD are still in the saccular phase of development, and the effects of LPS during this phase are poorly characterized. We hypothesized that chronic LPS exposure during the saccular phase disrupts lung development by mechanisms that promote inflammation and prevent optimal lung development and repair. Wild-type C57BL6J mice were intraperitoneally administered 3, 6, or 10 mg/kg of LPS or a vehicle once daily on postnatal days (PNDs) 3–5. The lungs were collected for proteomic and genomic analyses and flow cytometric detection on PND6. The impact of LPS on lung development, cell proliferation, and apoptosis was determined on PND7. Finally, we determined differences in the LPS effects between the saccular and alveolar lungs. LPS decreased the survival and growth rate and lung development in a dose-dependent manner. These effects were associated with a decreased expression of proteins regulating cell proliferation and differentiation and increased expression of those mediating inflammation. While the lung macrophage population of LPS-treated mice increased, the T-regulatory cell population decreased. Furthermore, LPS-induced inflammatory and apoptotic response and interruption of cell proliferation and alveolarization was greater in alveolar than in saccular lungs. Collectively, the data support our hypothesis and reveal several potential therapeutic targets for sepsis-mediated BPD in infants.

Original languageEnglish (US)
Pages (from-to)L229-L244
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume316
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • Bronchopulmonary dysplasia
  • Inflammation
  • Lipopolysaccharide
  • Proteomics
  • T-regulatory cells

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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