Bombesin-like peptides and mast cell responses: relevance to bronchopulmonary dysplasia?

Am J Respir Crit Care Med. 2003 Sep 1;168(5):601-11. doi: 10.1164/rccm.200212-1434OC. Epub 2003 Jun 13.


Bombesin-like peptides (BLPs) are elevated in newborns who later develop bronchopulmonary dysplasia (BPD). In baboon models, anti-BLP blocking antibodies abrogate BPD. We now demonstrate hyperplasia of both neuroendocrine cells and mast cells in lungs of baboons with BPD, compared with non-BPD controls or BLP antibody-treated BPD baboons. To determine whether BLPs are proinflammatory, bombesin was administered intratracheally to mice. Forty-eight hours later, we observed increased numbers of lung mast cells. We analyzed murine mast cells for BLP receptor gene expression, and identified mRNAs encoding bombesin receptor subtype 3 and neuromedin-B receptor (NMB-R), but not gastrin-releasing peptide receptor. Only NMB-R-null mice accumulated fewer lung mast cells after bombesin treatment. Bombesin, gastrin-releasing peptide, NMB, and a bombesin receptor subtype 3-specific ligand induced mast cell proliferation and chemotaxis in vitro. These observations support a role for multiple BLPs in promoting mast cell responses, suggesting a mechanistic link between BLPs and chronic inflammatory lung diseases.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bombesin / adverse effects*
  • Bombesin / pharmacology*
  • Bronchopulmonary Dysplasia / etiology*
  • Bronchopulmonary Dysplasia / pathology
  • Bronchopulmonary Dysplasia / physiopathology*
  • Cytokines / adverse effects
  • Cytokines / pharmacology
  • Disease Models, Animal
  • Female
  • Humans
  • In Vitro Techniques
  • Infant, Newborn
  • Inflammation Mediators / adverse effects*
  • Inflammation Mediators / pharmacology*
  • Lung / drug effects
  • Lung / pathology
  • Lung / physiopathology
  • Mast Cells / drug effects*
  • Mast Cells / pathology
  • Mast Cells / physiology*
  • Mice
  • Neurosecretory Systems / drug effects
  • Neurosecretory Systems / pathology
  • Neurosecretory Systems / physiopathology
  • Papio


  • Cytokines
  • Inflammation Mediators
  • Bombesin