Khalmuratova R, Lee M, Kim D W, Park J-W, Shin H-W
Department of Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Science, Ischemic/Hypoxic Disease Institute, Seoul National University Graduate School, Seoul, Republic of Korea.
Allergol Immunopathol (Madr). 2016 Jan-Feb;44(1):66-75. doi: 10.1016/j.aller.2015.04.004. Epub 2015 Aug 1.
The murine polyp model was developed previously using ovalbumin and Staphylococcus aureus enterotoxin B (SEB). Here, we established a model mimicking key aspects of chronic eosinophilic rhinosinusitis with nasal polyps using the house dust mite (HDM), a clinically relevant aeroallergen, co-administered with SEB. We assessed the inflammatory response and formation of nasal polypoid lesions in an experimental murine model using intranasal delivery of HDM and ovalbumin.
After induction of HDM-induced allergic rhinosinusitis in C57BL/6 mice, SEB (10ng) was instilled into the nasal cavity of mice for eight weeks. Phosphate-buffered saline-challenged mice served as control. Histopathological changes were evaluated using haematoxylin and eosin for overall inflammation, Sirius red for eosinophils, and periodic acid-Schiff stain for goblet cells. The distribution of mast cells in mouse nasal tissue was determined by immunohistochemistry. Serum total IgE was measured using enzyme-linked immunosorbent assay.
Compared to mice treated with HDM only, the HDM+SEB-treated mice demonstrated nasal polypoid lesion formation and a significant increase in the number of secretory cells and eosinophilic infiltration. Moreover, mice challenged intranasally with HDM showed highly abundant mast cells in the nasal mucosa. In contrast, OVA+SEB-challenged mice showed a significantly lower degree of mast cell infiltration.
We established an in vivo model of chronic allergic rhinosinusitis with nasal polypoid lesions using HDM aeroallergen. This study demonstrated that the HDM+SEB-induced murine polyp model could be utilised as a suitable model for nasal polyps, especially with both eosinophil and mast cell infiltration.
先前使用卵清蛋白和金黄色葡萄球菌肠毒素B(SEB)建立了小鼠息肉模型。在此,我们使用屋尘螨(HDM,一种临床相关的空气变应原)与SEB联合给药,建立了一种模拟伴有鼻息肉的慢性嗜酸性粒细胞性鼻-鼻窦炎关键特征的模型。我们使用鼻内给予HDM和卵清蛋白的方法,在实验性小鼠模型中评估了炎症反应和鼻息肉样病变的形成。
在C57BL/6小鼠中诱导HDM诱导的变应性鼻-鼻窦炎后,将SEB(10纳克)滴入小鼠鼻腔,持续8周。用磷酸盐缓冲盐水激发的小鼠作为对照。使用苏木精和伊红评估总体炎症的组织病理学变化,用天狼星红评估嗜酸性粒细胞,用高碘酸-希夫染色评估杯状细胞。通过免疫组织化学确定小鼠鼻组织中肥大细胞的分布。使用酶联免疫吸附测定法测量血清总IgE。
与仅用HDM治疗的小鼠相比,HDM + SEB治疗的小鼠表现出鼻息肉样病变形成,分泌细胞数量和嗜酸性粒细胞浸润显著增加。此外,经鼻内给予HDM激发的小鼠鼻黏膜中肥大细胞高度丰富。相比之下,OVA + SEB激发的小鼠肥大细胞浸润程度明显较低。
我们使用HDM变应原建立了伴有鼻息肉样病变的慢性变应性鼻-鼻窦炎的体内模型。本研究表明,HDM + SEB诱导的小鼠息肉模型可作为鼻息肉的合适模型,尤其是伴有嗜酸性粒细胞和肥大细胞浸润的情况。