Nell M J, Albers-Op 't Hof B M, Koerten H K, Grote J J
Department of Otorhinolaryngology, Leiden University Medical Center, The Netherlands.
Am J Otol. 2000 Sep;21(5):625-30.
HYPOTHESIS/BACKGROUND: Endotoxin can induce morphologic changes to middle ear epithelium, which can disturb the mucociliary clearance system (MCS) and lead to otitis media with effusion (OME). The bactericidal/permeability-increasing (BPI) protein is a major component of neutrophil granules and binds with high affinity to endotoxin. In this study, the capacity to inhibit the effects of endotoxin by rBPI21, a recombinant amino-terminal analog derived from BPI, was investigated on cultured human middle ear epithelium using light microscopy and scanning- and transmission electron microscopy.
Human middle ear epithelium was air-exposed cultured on a collagenous underlayer with different additions of endotoxin and rBPI21 to the culture medium. The tissue specimens were inspected after 4 weeks for the number of ciliated and secretory cells, thickness of the mucosal layer, and cell size.
The morphologic changes induced by endotoxin were increased thickness of the mucosal layer and increased number of secretory cells. These changes were significantly diminished or even absent when endotoxin was added with rBPI21 to the culture medium.
rBPI21 can inhibit morphologic changes in the middle ear epithelium due to endotoxin. Hence, the authors believe that rBPI21 can be a new therapeutic agent in the treatment of OME.
假说/背景：内毒素可诱导中耳上皮发生形态学改变，这会扰乱黏液纤毛清除系统（MCS）并导致分泌性中耳炎（OME）。杀菌/通透性增加蛋白（BPI）是中性粒细胞颗粒的主要成分，能与内毒素高亲和力结合。在本研究中，使用光学显微镜、扫描电子显微镜和透射电子显微镜，研究了源自BPI的重组氨基末端类似物rBPI21抑制内毒素对培养的人中耳上皮细胞作用的能力。
将人中耳上皮在胶原底层上进行空气暴露培养，在培养基中添加不同量的内毒素和rBPI21。4周后检查组织标本，观察纤毛细胞和分泌细胞数量、黏膜层厚度及细胞大小。
内毒素诱导的形态学改变包括黏膜层厚度增加和分泌细胞数量增多。当培养基中同时添加内毒素和rBPI21时，这些改变显著减轻甚至消失。
rBPI21可抑制内毒素引起的中耳上皮形态学改变。因此，作者认为rBPI21可成为治疗OME的新型治疗药物。
