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Bombesin-like peptides modulate alveolarization and angiogenesis in bronchopulmonary dysplasia

Meera Subramaniam1, Christine Bausch, Anne Twomey

  • 1Department of Medicine, Pulmonary Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

American Journal of Respiratory and Critical Care Medicine
|June 23, 2007
PubMed

Insights

Elevated bombesin-like peptides in premature baboons predicted lung injury, and blocking these peptides with 2A11 improved lung development and alveolarization, offering a potential BPD prevention strategy.

Area of Science:

  • Neonatal Physiology
  • Pulmonary Medicine
  • Developmental Biology

Background:

  • Bronchopulmonary dysplasia (BPD) incidence is rising despite advances in neonatal care.
  • Elevated bombesin-like peptide levels are observed in infants who develop BPD.
  • A previous study showed anti-bombesin antibody 2A11 mitigated lung injury in a 140-day hyperoxic baboon model.

Purpose of the Study:

  • To test if bombesin-like peptides mediate BPD in extremely premature baboons (125-day gestational age).
  • To evaluate the efficacy of anti-bombesin antibody 2A11 in a "modern-day BPD" model.

Main Methods:

  • Premature baboons (125-day gestational age) were treated with 2A11 on postnatal days 1, 3, and 6.
  • Lung histopathology was analyzed on postnatal days 14 and 21 for alveolarization.
  • Bombesin's regulation of angiogenesis was assessed using cultured pulmonary microvascular endothelial cells.

Main Results:

  • Urine bombesin-like peptide levels at postnatal days 2-3 correlated with impaired lung function at postnatal day 14.
  • Gastrin-releasing peptide mRNA was significantly elevated in 125-day PRN animals.
  • 2A11 treatment reduced alveolar wall thickness and improved alveolarization metrics (mean linear intercepts, branch points) by postnatal day 21.
  • Bombesin promoted endothelial cell tubulogenesis in vitro, an effect abrogated by co-cultured mesenchymal cells.

Conclusions:

  • Early overproduction of bombesin-like peptides predicts later alveolarization defects in premature baboons.
  • Blockade of bombesin-like peptides with 2A11 significantly improved lung septation and alveolarization.
  • These findings suggest a potential therapeutic strategy for preventing BPD in premature infants.
Abstract

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