The Temporal Evolution of Airways Hyperresponsiveness and Inflammation.
The Temporal Evolution of Airways Hyperresponsiveness and Inflammation.
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DOI：
10.4172/2155-6121.s1-005
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发表时间：
2012-01-25
期刊：
影响因子：
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通讯作者：
Lundblad LK
中科院分区：
文献类型：
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作者：
Riesenfeld E;Allen GB;Bates JH;Poynter ME;Wu M;Aimiand S;Lundblad LK
在哮喘小鼠模型中，气道高反应性（AHR）通常在首次抗原暴露后数天内产生。此外，持续的抗原攻击最终导致AHR表型的消退。人类哮喘也会随着时间的推移而加重和减弱，这表明研究过敏小鼠中AHR的时间过程将提供对哮喘患者症状变化的见解。在第0天和第14天用卵清蛋白（OVA）致敏小鼠。如通过气道阻力（Rn）、肺弹性（H）和组织阻尼（G）评估的，在先前在第21-23天攻击的小鼠中，在第21天OVA吸入后（短攻击组）、在第25天OVA吸入三天后（标准攻击组）和在第55天OVA吸入后（回忆攻击组）测量AHR。分析支气管肺泡灌洗的炎性细胞、细胞因子和蛋白质。短时间激发组的AHR特征为灌洗液中Rn和中性粒细胞积聚增加。标准激发组的AHR特征为H和G增加，但Rn仅为中度反应，而炎症为嗜酸性粒细胞。在标准激发方案中，缺乏纤维蛋白原的小鼠在其AHR应答方面与对照组没有差异。回忆激发组的AHR特征为仅G和H增加以及中性粒细胞和嗜酸性粒细胞数量增加。灌洗细胞因子仅在回忆激发组中升高。所有组的灌洗液蛋白均显著升高。过敏性炎症小鼠的表型随着时间的推移而明显演变，无论是在炎症的性质和AHR反应的位置方面。AHR小鼠模型的研究可能更好地集中在这种变化，而不是简单地在一个单一的时间点，在AHR是最大的。
Airways hyperresponsiveness (AHR) is usually produced within days of first antigen exposure in mouse models of asthma. Furthermore, continual antigen challenge eventually results in the resolution of the AHR phenotype. Human asthma also waxes and wanes with time, suggesting that studying the time course of AHR in the allergic mouse would offer insights into the variation in symptoms seen in asthmatics. Mice were sensitized with ovalbumin (OVA) on days 0 and 14. As assessed by airway resistance (Rn), lung elastance (H) and tissue damping (G), AHR was measured post an OVA inhalation on day 21 (Short Challenge group), after three days of OVA inhalation on day 25 (Standard Challenge group) and following an OVA inhalation on day 55 in mice previously challenged on days 21–23 (Recall Challenge group). Bronchoalveolar lavage was analyzed for inflammatory cells, cytokines and protein. AHR in the Short Challenge group was characterized by an increase in Rn and neutrophil accumulation in the lavage. AHR in the Standard Challenge group was characterized by increases in H and G but by only a modest response in Rn, while inflammation was eosinophilic. In the Standard Challenge protocol, mice lacking fibrinogen were no different from control in their AHR response. AHR in the Recall Challenge group was characterized by increases only in G and H and elevated numbers of both neutrophils and eosinophils. Lavage cytokines were only elevated in the Recall Challenge group. Lavage protein was significantly elevated in all groups. The phenotype in allergically inflamed mice evolves distinctly over time, both in terms of the nature of the inflammation and the location of the AHR response. The study of mouse models of AHR might be better served by focusing on this variation rather than simply on a single time point at which AHR is maximal.