Subramaniam Meera, Sugiyama Kumiya, Coy David H, Kong Yanping, Miller York E, Weller Peter F, Wada Keiji, Wada Etsuko, Sunday Mary E
Brigham and Women's Hospital, Department of Pathology, 75 Francis Street, Boston, MA 02115, USA.
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.
类蛙皮素样肽（BLPs）在后来发展为支气管肺发育不良（BPD）的新生儿中水平升高。在狒狒模型中，抗BLP阻断抗体可消除BPD。与非BPD对照或BLP抗体治疗的BPD狒狒相比，我们现在证明了患有BPD的狒狒肺中神经内分泌细胞和肥大细胞均增生。为了确定BLPs是否具有促炎作用，将蛙皮素经气管内给予小鼠。48小时后，我们观察到肺肥大细胞数量增加。我们分析了鼠肥大细胞的BLP受体基因表达，并鉴定出编码蛙皮素受体亚型3和神经介素B受体（NMB-R）的mRNA，但未鉴定出胃泌素释放肽受体。蛙皮素治疗后，只有NMB-R基因敲除小鼠的肺肥大细胞积累较少。蛙皮素、胃泌素释放肽、NMB和一种蛙皮素受体亚型3特异性配体在体外诱导肥大细胞增殖和趋化性。这些观察结果支持多种BLPs在促进肥大细胞反应中的作用，提示BLPs与慢性炎症性肺病之间存在机制联系。
