Bombesin inhibits alveolarization and promotes pulmonary fibrosis in newborn mice.

Journal Article (Journal Article)

RATIONALE: Bombesin-like peptides promote fetal lung development. Normally, levels of mammalian bombesin (gastrin-releasing peptide [GRP]) drop postnatally, but these levels are elevated in newborns that develop bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by arrested alveolarization. In premature baboons with BPD, antibombesin antibodies reduce lung injury and promote alveolarization. OBJECTIVES: The present study tests whether exogenous bombesin or GRP given perinatally alters alveolar development in newborn mice. METHODS: Mice were given peptides intraperitoneally twice daily on Postnatal Days 1-3. On Day 14 lungs were inflation-fixed for histopathologic analyses of alveolarization. MEASUREMENTS AND MAIN RESULTS: Bombesin had multiple effects on Day 14 lung, when alveolarization was about half complete. First, bombesin induced alveolar myofibroblast proliferation and increased alveolar wall thickness compared with saline-treated control animals. Second, bombesin diminished alveolarization in C57BL/6 (but not Swiss-Webster) mice. We used receptor-null mice to explore which receptors might mediate these effects. Compared with wild-type littermates, bombesin-treated GRP receptor (GRPR)-null mice had increased interstitial fibrosis but reduced defects in alveolarization. Neuromedin B (NMB) receptor-null and bombesin receptor subtype 3-null mice had the same responses as their wild-type littermates. GRP had the same effects as bombesin, whereas neither NMB nor a synthetic bombesin receptor type 3 ligand had any effect. All effects of GRP were abrogated in GRPR-null mice. CONCLUSIONS: Bombesin/GRP can induce features of BPD, including interstitial fibrosis and diminished alveolarization. GRPR appears to mediate all effects of GRP, but only part of the bombesin effect on alveolarization, suggesting that novel receptors may mediate some effects of bombesin in newborn lung.

Full Text

Duke Authors

Cited Authors

  • Ashour, K; Shan, L; Lee, JH; Schlicher, W; Wada, K; Wada, E; Sunday, ME

Published Date

  • June 15, 2006

Published In

Volume / Issue

  • 173 / 12

Start / End Page

  • 1377 - 1385

PubMed ID

  • 16603607

Pubmed Central ID

  • PMC2662976

International Standard Serial Number (ISSN)

  • 1073-449X

Digital Object Identifier (DOI)

  • 10.1164/rccm.200507-1014OC


  • eng

Conference Location

  • United States