Published ahead of print on June 13, 2003, doi:10.1164/rccm.200212-1434OC Am. J. Respir. Crit. Care Med., Volume 168, Number 5, September 2003, 601-611 A more recent version of this article appeared on September 1, 2003
Submitted on December 16, 2002 BOMBESIN-LIKE PEPTIDES AND MAST CELL RESPONSES: RELEVANCE TO BRONCHOPULMONARY DYSPLASIA?Meera Subramaniam1,1 Pathology, Children's Hospital, Boston, MA, USA, 2 Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA, 3 Medicine, Tulane University Health Sciences, New Orleans, LA, USA, 4 Medicine, University of Colorado, VA Medical Center, Denver, CO, USA, 5 Neurodegenerative Diseases, Institute of Neuroscience, Tokyo, Japan, 6 Pathology, Brigham and Women's and Children's Hospitals, Boston, MA, USA; Neurodegenerative Diseases, Institute of Neuroscience, Tokyo, Japan * To whom correspondence should be addressed. E-mail: sunday{at}tch.harvard.ed.
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 to non-BPD controls or BLP antibody-treated BPD baboons. To determine whether BLPs are pro-inflammatory, bombesin was administered intratracheally to mice. 48 hours later, we observed increased numbers of lung mast cells. We analyzed murine mast cells for BLP receptor gene expression, and identified mRNAs encoding BRS-3 (bombesin-receptor-subtype-3) and neuromedin-B receptor (NMB-R), but not gastrin-releasing peptide receptor (GRP-R). Only NMB-R-null mice accumulated fewer lung mast cells following bombesin treatment. Bombesin, GRP, NMB and a BRS-3-specific ligand (BRS-3L) 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. Key words: Infant, premature; neuromedin B; chemotaxis; pulmonary fibrosis
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
