Innate immune responses and neuroepithelial degeneration and regeneration in the mouse olfactory mucosa induced by intranasal administration of Poly(I:C).
Innate immune responses and neuroepithelial degeneration and regeneration in the mouse olfactory mucosa induced by intranasal administration of Poly(I:C).
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DOI：
10.1007/s00441-014-1848-2
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发表时间：
2014-07
影响因子：
3.6
通讯作者：
Yamasoba, Tatsuya
中科院分区：
文献类型：
--
作者：
Kanaya, Kaori;Kondo, Kenji;Suzukawa, Keigo;Sakamoto, Takashi;Kikuta, Shu;Okada, Kazunari;Yamasoba, Tatsuya
病毒后嗅觉障碍（PVOD）的发病机制尚未完全阐明。我们研究了鼻内注射病毒双链RNA的合成类似物聚肌胞苷酸[Poly（I：C）]诱导的小鼠嗅粘膜的形态学变化和先天性免疫应答。小鼠接受三次含或不含Poly（I：C）的盐水给药，每24小时一次。在第一次给药后的不同时间间隔（8小时，3，9和24天）收集嗅粘膜。Poly（I：C）组嗅神经上皮凋亡细胞数在8 h时已明显增多。在第9天，嗅觉神经上皮严重退化，行为测试表明小鼠表现出嗅觉退化的迹象。在24天时，神经上皮的结构几乎完全再生。关于先天性免疫反应，许多中性粒细胞在8 h时已浸润嗅神经上皮，并在3 d时渗出到鼻腔中。在8 h时，巨噬细胞也浸润了嗅神经上皮，尽管程度较轻，但在24 d时它们仍保留在神经上皮中。Poly（I：C）诱导的神经上皮损伤被中性粒细胞弹性蛋白酶抑制剂显著抑制，并且在血小板减少模型小鼠中被抑制。这些结果表明，由嗜中性粒细胞介导的先天性免疫反应引起的继发性损伤在PVOD的发病机制中起重要作用。
The pathogenesis of postviral olfactory disorder (PVOD) has not been fully elucidated. We investigated morphological changes and innate immune responses in the mouse olfactory mucosa induced by intranasal administration of polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic analog of viral double-stranded RNA. Mice received three administrations of saline with or without Poly(I:C), once every 24 h. The olfactory mucosa was harvested at various intervals after the first administration (8 h, 3, 9 and 24 days). In the Poly(I:C) group, the number of apoptotic cells in the olfactory neuroepithelium had increased at 8 h. At 9 days, the olfactory neuroepithelium had severely degenerated and behavioral tests demonstrated that the mice showed signs of olfactory deterioration. At 24 days, the structure of the neuroepithelium had regenerated almost completely. Regarding the innate immune responses, many neutrophils had infiltrated the olfactory neuroepithelium at 8 h and had exuded into the nasal cavity by 3 days. Macrophages had also infiltrated the olfactory neuroepithelium at 8 h although to a lesser extent, but they still remained in the neuroepithelium at 24 days. Poly(I:C)-induced neuroepithelial damage was significantly inhibited by a neutrophil elastase inhibitor and was suppressed in neutropenic model mice. These findings suggest that the secondary damage caused by the neutrophil-mediated innate immune response plays an important role in the pathogenesis of PVOD.
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影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
1.5
作者：
GENTER, MB;DEAMER, NJ;LEVI, PE
通讯作者：
LEVI, PE
DOI：
10.1165/rcmb.2002-0055oc
发表时间：
2003-06-01
影响因子：
6.4
作者：
Gern, JE;French, DA;Busse, WW
通讯作者：
Busse, WW
影响因子：
64.8
作者：
Kobayakawa, Ko;Kobayakawa, Reiko;Sakano, Hitoshi
通讯作者：
Sakano, Hitoshi
影响因子：
--
作者：
GETCHELL, ML;GETCHELL, TV
通讯作者：
GETCHELL, TV