Bombesin-like peptides and mast cell responses: relevance to bronchopulmonary dysplasia?
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.
Subramaniam
Meera
M
Brigham and Women's Hospital, Department of Pathology, 75 Francis Street, Boston, MA 02115, USA.
Sugiyama
Kumiya
K
Coy
David H
DH
Kong
Yanping
Y
Miller
York E
YE
Weller
Peter F
PF
Wada
Keiji
K
Wada
Etsuko
E
Sunday
Mary E
ME
D000818:Animals; D001839:Bombesin / Q000009:adverse effects* / Q000494:pharmacology*; D001997:Bronchopulmonary Dysplasia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D016207:Cytokines / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000009:adverse effects* / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008407:Mast Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D051379:Mice; D009490:Neurosecretory Systems / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010215:Papio
D016207:Cytokines; D018836:Inflammation Mediators; D001839:Bombesin