Intranasal Administration of Semaphorin-3A Alleviates Sneezing and Nasal Rubbing in a Murine Model of Allergic Rhinitis
Intranasal Administration of Semaphorin-3A Alleviates Sneezing and Nasal Rubbing in a Murine Model of Allergic Rhinitis
复制标题
DOI：
10.1254/jphs.11005fp
复制
发表时间：
2011-09-01
影响因子：
3.5
通讯作者：
Ikezawa, Zenro
中科院分区：
文献类型：
--
作者：
Sawaki, Haruna;Nakamura, Fumio;Ikezawa, Zenro
打喷嚏和鼻粘膜持续瘙痒是过敏性鼻炎（AR）的痛苦症状。最近的研究表明，超神经支配的感觉神经元在鼻甲是打喷嚏和瘙痒的根本原因之一。由于Semaphorin-3A（Sema 3A）先前已显示限制感觉神经元的神经支配，因此推测鼻粘膜中Sema 3A表达的减少可能有助于超敏反应。卵清蛋白致敏AR小鼠模型的分析表明，鼻上皮中Sema 3A的表达减少，这伴随着鼻甲骨固有层中神经纤维密度的增加。在补救实验中，AR模型小鼠鼻内施用重组Sema 3A减轻了打喷嚏和擦鼻症状。此外，组织学检查还显示，神经纤维密度下降，在固有层的Sema 3A处理的鼻甲。这些结果表明，鼻过敏性变应性鼻炎可能是由于减少Sema 3A的表达和鼻内给药的Sema 3A可能提供了一种新的方法，以减轻过敏性变应性鼻炎的治疗症状。
Sneezing and persistent itching of the nasal mucosa are distressing symptoms of allergic rhinitis (AR). Recent studies have revealed that hyperinnervation of sensory neurons in the nasal turbinate is one of the underlying causes of sneezing and itching. Since Semaphorin-3A (Sema3A) has been previously shown to restrict innervation of sensory neurons, it is presumed that reduced Sema3A expression in the nasal mucosa might contribute to the hypersensitivity. Analysis of the mouse model of ovalbumin-sensitized AR demonstrated a decreased expression of Sema3A in the nasal epithelium, which was accompanied by an increased nerve fiber density in the lamina propria of the turbinate. In rescue experiments, intranasal administration of recombinant Sema3A in the AR model mice alleviated sneezing and nasal rubbing symptoms. In addition, histological examinations also revealed that nerve fiber density was decreased in the lamina propria of the Sema3A-treated nasal turbinate. These results suggest that the nasal hypersensitivity of AR may be attributed to reduction of Sema3A expression and intranasal administration of Sema3A may provide a novel approach to alleviate the allergic symptoms for AR treatment.