Contribution of allergen-specific and nonspecific nasal responses to early-phase and late-phase nasal responses
Contribution of allergen-specific and nonspecific nasal responses to early-phase and late-phase nasal responses
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DOI：
10.1016/j.jaci.2007.11.002
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发表时间：
2008-03-01
影响因子：
14.2
通讯作者：
Gelfand, Erwin W.
中科院分区：
文献类型：
--
作者：
Miyahara, Satoko;Miyahara, Nobuaki;Gelfand, Erwin W.
背景资料：过敏原特异性早期鼻反应和非特异性鼻反应以及肥大细胞对变应性鼻炎病理生理学的相对贡献还没有很好的定义。目的：使用变应性鼻炎小鼠模型确定特异性反应、非特异性反应和肥大细胞对早期和晚期反应发展的贡献。致敏的野生型和Fc β RI缺陷型（FC β RI-/-）小鼠暴露于过敏原3、5或12天。作为鼻反应性的指标，呼吸频率和鼻阻力monitored.Results：致敏小鼠暴露于3天的鼻变应原的挑战表现出非特异性的早期反应。随着过敏原暴露次数的增加，非特异性反应逐渐减少，过敏原特异性早期反应和晚期反应增加。致敏的Fc ε RI-/-小鼠没有产生非特异性鼻反应或晚期反应，但是将体外分化的野生型肥大细胞转移到Fc ε RI-/-小鼠中恢复了非特异性早期鼻反应，但没有恢复晚期反应。这些数据表明，非特异性鼻反应是早期反应的主要因素，特别是在最初的过敏原暴露期间，并且依赖于肥大细胞。增加过敏原暴露导致过敏原特异性反应增加，将非特异性早期反应转化为过敏原特异性和肥大细胞无关的晚期反应。
Background: The relative contributions of the allergen-specific early-phase nasal response and nonspecific nasal response and mast cells to the pathophysiology of allergic rhinitis are not well defined.Objectives: To determine the contributions of specific reactivity, nonspecific reactivity, and mast cells to the development of early-phase and late-phase responses using a mouse model of allergic rhinitis.Methods: Sensitized wild-type and Fc epsilon RI-deficient (FC epsilon RI-/-) mice were exposed to allergen for 3, 5, or 12 days. As indicators of nasal reactivity, respiratory frequency and nasal resistance were monitored.Results: Sensitized mice exposed to 3 days of nasal allergen challenge showed a nonspecific early-phase response. As the number of allergen exposures increased, there was progressive diminution in nonspecific responses with increased allergen-specific early-phase responses and a late-phase response. Sensitized Fc epsilon RI-/- mice did not develop nonspecific nasal responses or late-phase responses, but transfer of in vitro-differentiated wild-type mast cells into Fc epsilon RI-/- mice restored nonspecific early-phase nasal responses but not the late-phase response.Conclusion: These data identify the nonspecific nasal response as a major contributor to the early-phase response, especially during initial allergen exposure, and is dependent on mast cells. Increasing allergen exposure results in increasing allergen-specific responses, converting the nonspecific early-phase response to a late-phase response that is allergen-specific and mast cell-independent.