Division of Neonatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Am J Respir Cell Mol Biol. 2011 Sep;45(3):550-6. doi: 10.1165/rcmb.2010-0376OC. Epub 2010 Dec 22.
Inflammation plays a key role in the pathogenesis of bronchopulmonary dysplasia (BPD). Fatty acid-binding proteins (FABPs) 4 and 5 regulate the inflammatory activity of macrophages. Whether FABPs 4 and 5 could play a role in the pathogenesis of BPD via the promotion of macrophage inflammatory activity is unknown. This study sought to examine whether the expression levels of FABP4 and FABP5 were altered in bronchoalveolar lavage fluid and lung tissue in a baboon model of BPD. This study also sought to characterize the cell types that express these proteins. Real-time PCR, immunoblotting, immunohistochemistry, and double immunofluorescence were used to examine the expression of FABPs in samples of BPD. Morphometric analysis was used to quantify FABP4-positive peribronchial blood vessels in lung sections. FABP4 was primarily expressed in macrophages in samples of BPD. In addition, FABP4 was expressed in the endothelial cells of blood vessels in peribronchial areas and the vasa vasorum, but not in the alveolar vasculature in samples of BPD. FABP4 concentrations were significantly increased in lungs and bronchoalveolar lavage fluid samples with BPD. An increased density of FABP4-positive peribronchial blood vessels was evident in both baboon and human BPD sections. FABP5 was expressed in several cell types, including alveolar epithelial cells and macrophages. FABP5 concentrations did not show any significant alterations in BPD. In conclusion, FABP4 but not FABP5 levels are increased in BPD. FABP4 is differentially expressed in endothelial cells of the bronchial microvasculature, which demonstrates a previously unrecognized expansion in BPD.
炎症在支气管肺发育不良(BPD)的发病机制中起关键作用。脂肪酸结合蛋白(FABP)4 和 5 调节巨噬细胞的炎症活性。FABP4 和 5 是否可以通过促进巨噬细胞炎症活性在 BPD 的发病机制中发挥作用尚不清楚。本研究旨在检查 FABP4 和 FABP5 的表达水平是否在狒狒 BPD 模型的肺泡灌洗液和肺组织中发生改变。本研究还试图描述表达这些蛋白的细胞类型。实时 PCR、免疫印迹、免疫组织化学和双重免疫荧光用于检查 BPD 样本中 FABP 的表达。形态计量分析用于定量肺组织切片中 FABP4 阳性的细支气管周围血管。FABP4 主要在 BPD 样本中的巨噬细胞中表达。此外,FABP4 在细支气管周围区域和血管腔中的血管内皮细胞中表达,但在 BPD 的肺泡脉管系统中不表达。FABP4 浓度在患有 BPD 的肺和肺泡灌洗液样本中显着增加。在狒狒和人类 BPD 切片中均可见 FABP4 阳性细支气管周围血管的密度增加。FABP5 在几种细胞类型中表达,包括肺泡上皮细胞和巨噬细胞。BPD 中 FABP5 浓度没有明显变化。总之,BPD 中 FABP4 而不是 FABP5 水平增加。FABP4 在支气管微血管的内皮细胞中差异表达,这表明在 BPD 中存在以前未被认识到的扩张。