title: Gastrin-releasing peptide, immune responses, and lung disease.
abstract: Gastrin-releasing peptide (GRP) is produced by pulmonary neuroendocrine cells (PNECs), with highest numbers of GRP-positive cells present in fetal lung. Normally GRP-positive PNECs are relatively infrequent after birth, but PNEC hyperplasia is frequently associated with chronic lung diseases. To address the hypothesis that GRP mediates chronic lung injury, we present the cumulative evidence implicating GRP in bronchopulmonary dysplasia (BPD), the chronic lung disease of premature infants who survive acute respiratory distress syndrome. The availability of well-characterized animal models of BPD was a critical tool for demonstrating that GRP plays a direct role in the early pathogenesis of this disease. Potential mechanisms by which GRP contributes to injury are analyzed, with the main focus on innate immunity. Autoreactive T cells may contribute to lung injury late in the course of disease. A working model is proposed with GRP triggering multiple cell types in both the innate and adaptive immune systems, promoting cascades culminating in chronic lung disease. These observations represent a paradigm shift in the understanding of the early pathogenesis of BPD, and suggest that GRP blockade could be a novel treatment to prevent this lung disease in premature infants.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Degan
authors.forename: Giselle Y
authors.initials: GY
authors.lastname: Lopez
authors.forename: Katharine
authors.initials: K
authors.lastname: Kevill
authors.forename: Mary E
authors.initials: ME
authors.lastname: Sunday
mesh_terms: D000818:Animals; D001839:Bombesin / Q000378:metabolism; D001997:Bronchopulmonary Dysplasia / Q000276:immunology* / Q000378:metabolism; D019886:Gastrin-Releasing Peptide / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D055633:Immune System Phenomena; D007113:Immunity, Innate; D007231:Infant, Newborn; D008171:Lung Diseases / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D019886:Gastrin-Releasing Peptide; D001839:Bombesin