Enhanced allergic Eustachian tube response in surfactant protein D knockout mice induced by ovalbumin
Background: Allergic reactions have been widely recognized as closely associated with the development of Eustachian tube dysfunction (ETD). However, the precise pathophysiological mechanisms remain unclear, and effective models to elucidate the role of allergic responses in ETD are lacking. Surfacta...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
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| Series: | World Allergy Organization Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1939455125000389 |
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| Summary: | Background: Allergic reactions have been widely recognized as closely associated with the development of Eustachian tube dysfunction (ETD). However, the precise pathophysiological mechanisms remain unclear, and effective models to elucidate the role of allergic responses in ETD are lacking. Surfactant protein D (SPD), an important immune defense factor in the Eustachian tube (ET), not only reduces surface tension but also exhibits anti-adhesion and inflammation-regulating properties. Nevertheless, the role of SPD in allergic inflammation of the ET has not been fully explored. Objective: This study aimed to investigate the morphological and functional changes in the ET induced by ovalbumin under SPD gene deficiency and to explore the underlying mechanisms. Methods: Experimental models were established using C57 mice with different SPD genotypes, divided into control groups (WT-PBS and SPD-KO-PBS) and allergic groups (WT-OVA and SPD-KO-OVA). Allergic symptoms were recorded following intraperitoneal OVA injection and nasal challenges, and serum total IgE levels were measured. Histological methods were used to evaluate the number and morphological changes of eosinophils in the ET. Immunostaining was performed to analyze the secretion of Muc5b and Muc5ac. ET function was assessed by measuring passive opening pressure (POP) and comparing active clearance of negative pressure (ACNP). Mucociliary clearance (MCC) was evaluated using small-animal imaging techniques. Exogenous SPD was administered intranasally to SPD-KO-OVA mice to evaluate therapeutic effects. Results: Allergic mice exhibited significant inflammatory features, including increased sneezing frequency, elevated serum IgE levels, eosinophil infiltration in the ET mucosa, goblet cell hyperplasia, and abnormal mucin secretion. Meanwhile, ACNP and MCC functions were significantly impaired. Compared with the WT-OVA group, SPD-KO-OVA mice demonstrated more severe eosinophil infiltration, thickened ET mucosa, enhanced mucus gland secretion, elevated POP, and further impaired ACNP and MCC functions, with excessive mucus accumulation in the middle ear cavity. Abnormal overexpression of Muc5ac and Muc5b may further exacerbate OVA-induced ET dysfunction. Intranasal SPD treatment significantly attenuated mucosal inflammation, reduced eosinophil infiltration and mucin production, and restored ACNP function in SPD-KO-OVA mice. Conclusions: SPD plays a critical role in regulating allergic inflammation and protecting ET function. Its deficiency exacerbates OVA-induced inflammation and functional impairment of the ET, while exogenous SPD administration ameliorates tissue inflammation and restores ACNP efficacy. These findings highlight SPD as a therapeutic target for allergic ETD. |
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| ISSN: | 1939-4551 |