Kim Dong-Young, Lee Sun Hye, Carter Roderick G, Kato Atsushi, Schleimer Robert P, Cho Seong H
1 Department of Medicine, Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
2 Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea.
Am J Respir Cell Mol Biol. 2016 Aug;55(2):170-5. doi: 10.1165/rcmb.2016-0002RC.
Animal model systems are invaluable for examining human diseases. Our laboratory recently established a mouse model of nasal polyps (NPs) and investigated similarities and differences between this mouse model and human NPs. We especially focus on the hypothesis that B cell activation occurs during NP generation in the murine model. After induction of ovalbumin-induced allergic rhinosinusitis, 6% ovalbumin and Staphylococcus aureus enterotoxin B (10 ng) were instilled into the nasal cavity of mice three times per week for 8 weeks. The development of structures that somewhat resemble NPs (which we will refer to as NPs) was confirmed by hematoxylin and eosin staining. The mRNA and protein levels of various inflammatory cell markers and mediators were measured by real-time PCR in nasal tissue and by ELISA in nasal lavage fluid (NLF), respectively. Total Ig isotype levels in NLF were also quantitated using the Mouse Ig Isotyping Multiplex kit (EMD Millipore, Billerica, MA) on a Luminex 200 instrument (Life Technologies, Grand Island, NY). Similar to human NPs, there were significant increases in gene expression of inflammatory cell markers, such as CD19, CD138, CD11c, and mast cell protease-6 in nasal tissue samples of the NP group compared with those of the control group. In further investigations of B cell activation, mRNA expressions of B cell activating factor and a proliferation-inducing ligand were found to be significantly increased in mouse NP tissue. B cell-activating factor protein concentration and IgA and IgG1 levels in NLF were significantly higher in the NP group compared with the control group. In this study, the NP mouse model demonstrated enhanced B cell responses, which are reminiscent of B cell responses in human NPs.
动物模型系统对于研究人类疾病而言非常宝贵。我们实验室最近建立了鼻息肉(NP)的小鼠模型,并研究了该小鼠模型与人类NP之间的异同。我们特别关注这样一个假说,即在小鼠模型中NP形成过程中会发生B细胞活化。在诱导卵清蛋白诱导的变应性鼻-鼻窦炎后,每周三次向小鼠鼻腔内滴注6%卵清蛋白和金黄色葡萄球菌肠毒素B(10 ng),持续8周。通过苏木精和伊红染色证实了形成了一些类似于NP(我们将其称为NP)的结构。分别通过实时PCR检测鼻组织中各种炎症细胞标志物和介质的mRNA水平,以及通过ELISA检测鼻灌洗液(NLF)中的水平。还使用Mouse Ig Isotyping Multiplex试剂盒(EMD Millipore,比勒里卡,马萨诸塞州)在Luminex 200仪器(Life Technologies,大岛,纽约州)上对NLF中的总Ig同种型水平进行定量。与人类NP相似,与对照组相比,NP组鼻组织样本中炎症细胞标志物如CD19、CD138、CD11c和肥大细胞蛋白酶-6的基因表达显著增加。在对B细胞活化的进一步研究中,发现小鼠NP组织中B细胞活化因子和增殖诱导配体的mRNA表达显著增加。与对照组相比,NP组NLF中B细胞活化因子蛋白浓度以及IgA和IgG1水平显著更高。在本研究中,NP小鼠模型表现出增强的B细胞反应,这让人联想到人类NP中的B细胞反应。