Wang Heng, Lu Xiang, Cao Ping-Ping, Chu Yan, Long Xiao-Bo, Zhang Xin-Hao, You Xue-Jun, Cui Yong-Hua, Liu Zheng
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Am J Rhinol. 2008 Jul-Aug;22(4):343-8. doi: 10.2500/ajr.2008.22.3184.
The purpose of this study was to elucidate histological and immunologic features of mouse models of bacterial chronic rhinosinusitis (BCRS) and allergic chronic rhinosinusitis (ACRS).
A BCRS mouse model was established using Streptococcus pneumoniae inoculation plus Merocel (Medtronic, Jacksonville, FL) ostiomeatal obstruction for 12 weeks. An ACRS mouse model was developed by means of ovalbumin (OVA) i.p. injection and subsequent repeated OVA intranasal challenge for 12 weeks. Histological changes of sinonasal mucosa of both models were examined by means of hematoxylin and eosin staining for general morphology and inflammatory cell, periodic acid-Schiff staining for goblet cell, and Masson-trichrome staining for collagen. Enzyme-linked immunosorbent assay was used to detect the concentrations of various cytokines in nasal lavage fluid.
Polymorphonuclear neutrophil infiltration in lamina propria was more obvious in the BCRS model, whereas eosinophil infiltration was more apparent in the ACRS model. Significant goblet cell and subepithelial gland hyperplasia, subepithelial fibrosis, epithelial thickening, and mononuclear cell infiltration were shown in both models with more severe extent found in the ACRS model. Interleukin (IL)-6 and tumor necrosis factor alpha levels in NLF from both models were increased and peaked at 1 week. Interferon gamma levels were also up-regulated in both models but reached maximum at 1 week in the BCRS model and 4 weeks in the ACRS model. IL-8 (CXCL8) levels were only increased in BCRS mice and peaked at 1 week, whereas IL-5, IL-13, and eotaxin (CCL11) levels were only enhanced in ACRS mice and peaked at 1 week. The Th1/Th2 ratio in BCRS mice was significantly higher than that in ACRS mice (6.68 +/- 2.33 versus 1.37 +/- 0.86; p < 0.01).
Histological and immunologic features of BCRS and ACRS mouse models were similar to those of human noneosinophilic and eosinophilic CRS, respectively. BCRS and ACRS mouse models have distinct immunologic characteristics and are applicable for CRS research.
本研究旨在阐明细菌性慢性鼻-鼻窦炎（BCRS）和变应性慢性鼻-鼻窦炎（ACRS）小鼠模型的组织学和免疫学特征。
采用肺炎链球菌接种加Merocel（美敦力公司，佛罗里达州杰克逊维尔）阻塞窦口鼻道复合体12周建立BCRS小鼠模型。通过腹腔注射卵清蛋白（OVA）并随后反复经鼻给予OVA刺激12周建立ACRS小鼠模型。采用苏木精-伊红染色观察两种模型鼻黏膜的大体形态和炎症细胞，过碘酸-希夫染色观察杯状细胞，Masson三色染色观察胶原，以检测两种模型鼻黏膜的组织学变化。采用酶联免疫吸附测定法检测鼻腔灌洗液中各种细胞因子的浓度。
BCRS模型固有层中多形核中性粒细胞浸润更明显，而ACRS模型中嗜酸性粒细胞浸润更明显。两种模型均显示杯状细胞和上皮下腺显著增生、上皮下纤维化、上皮增厚及单核细胞浸润，ACRS模型中这些改变程度更严重。两种模型鼻腔灌洗液中白细胞介素（IL）-6和肿瘤坏死因子α水平均升高，并在第1周达到峰值。两种模型中γ干扰素水平也上调，但在BCRS模型中于第1周达到最高，在ACRS模型中于第4周达到最高。IL-8（CXCL8）水平仅在BCRS小鼠中升高，并于第1周达到峰值，而IL-5、IL-13和嗜酸性粒细胞趋化因子（CCL11）水平仅在ACRS小鼠中升高，并于第1周达到峰值。BCRS小鼠的Th1/Th2比值显著高于ACRS小鼠（6.68±2.33对1.37±0.86；p<0.01）。
BCRS和ACRS小鼠模型的组织学和免疫学特征分别与人非嗜酸性和嗜酸性慢性鼻-鼻窦炎相似。BCRS和ACRS小鼠模型具有不同的免疫学特征，适用于慢性鼻-鼻窦炎的研究。
