Original ArticleInduction of nasal polyps using house dust mite and Staphylococcal enterotoxin B in C57BL/6 mice
Introduction
Chronic rhinosinusitis (CRS) encompasses a heterogeneous group of disorders defined by the inflammation of the paranasal sinuses and represents a significant health problem worldwide. CRS has been categorised typically as CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) based on endoscopic examination findings.1, 2 CRSwNP is characterised by inflammatory cell infiltration and structural modifications of the epithelium (secretary hyperplasia and squamous metaplasia) and lamina propria (basement membrane thickening, extracellular matrix accumulation and fibrosis). However, the underlying mechanisms interlinking these pathological conditions to nasal polyp formation remain unclear.3
To date, murine studies investigating CRS have employed systemic sensitisation and intranasal challenge with ovalbumin (OVA). Chronic challenge models in mice involve repeated exposure to antigen for up to 12 weeks. Low-dose Staphylococcal enterotoxin B (SEB) induced nasal polypoid lesions with increased eosinophilic infiltration in an allergic rhinosinusitis model.4 OVA challenge models of CRSwNP offer opportunities for increasing our understanding of the pathogenesis underlying this disease, as well as for identifying novel therapeutic targets, although more relevant allergens such as the house dust mite (HDM) may also be considered.5, 6
The HDM is ubiquitous in human habitats and is a significant factor underlying allergic rhinitis and allergic asthma. These features make it one of the important sources of indoor allergens.7, 8 The predominant HDMs isolated from dust samples are Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). Although HDM extracts are complex from an immunological perspective, they are ultimately more representative of real-life aeroallergen exposure.9, 10 Recently, common parameters of airway allergy such as airway inflammation, Th2 cytokine production and elevated Der f-specific IgE levels were shown in an intranasal HDM sensitisation mouse model.11, 12, 13 Despite the high prevalence of HDM allergy, the cellular and molecular networks that initiate and regulate this Th2-biased response have been investigated using only the OVA-induced polyp model.14
In this study, we established a model mimicking key aspects of CRSwNP using the clinically relevant aeroallergen HDM with co-administration of SEB. Additionally, we compared the immune-inflammatory and nasal polyp formation responses to intranasal delivery of HDM extract and OVA in the experimental murine model.
Section snippets
Experimental animals
Eighteen male C57BL/6 mice (4 weeks of age; 20–25 g each) were purchased from Central Laboratory Animal, Inc. (Seoul, Korea) and housed for one week before initiating experiments. The animals were kept in a pathogen-free biohazard containment facility maintained at 22–24 °C and 50–60% humidity. All experimental protocols complied with the Guidelines of the National Institute of Health and the Declaration of Helsinki, and were approved by the Committee on the Use and Care of Animals
The formation of nasal polypoid lesions
No polyp-like lesions were observed in groups A and B (Fig. 1B). Polypoid lesions were found only in mice that received SEB intranasally (groups C and D). Five lesions were observed in three of five mice in group C (Fig. 1C). Similarly, six lesions were evident in four of five mice in group D (Fig. 1D). Thickened mucosae with polyp-like lesions were observed primarily at the transition zone of the olfactory and respiratory epithelia. Morphological changes such as secretory hyperplasia as well
Discussion
The inflammatory response to intranasal delivery of HDM was characterised by infiltrate with a considerable proportion comprised of eosinophils and mast cells. Our data demonstrated that mast cells might play an important role in the generation of Th2 sensitisation and airway eosinophilic inflammation in C57BL/6 mice exposed to HDM extract in vivo. Yu and Chen17 demonstrated that Der f could rapidly activate mast cells in mice. Der f could trigger the release of mMCP-1 in mice 30 min after an
Conflict of interest
The authors have no conflict of interest to declare.
Funding
This work was supported by grant no 03-2014-0120 from the SNUH Research Fund, by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (0411-20130037), by the Education and Research Encouragement Fund of Seoul National University Hospital (2015), and by Research Resettlement Fund for the new faculty of Seoul National University.
Protection of human subjects and animals in research
Protection of human and animal subjects. The authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration.
Patients’ data protection
Confidentiality of Data. The authors declare that no patient data appear in this article.
Right to privacy and informed consent
Right to privacy and informed consent. The authors declare that no patient data appear in this article.
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