Differential effects of allergen challenge on large and small airway reactivity in mice.

Differential effects of allergen challenge on large and small airway reactivity in mice.
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DOI:
10.1371/journal.pone.0074101
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Bourke JE
Bourke JE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Donovan C;Royce SG;Esposito J;Tran J;Ibrahim ZA;Tang ML;Bailey S;Bourke JE

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大气道和小气道对哮喘高反应性的相对作用尚未得到充分评估。本研究采用慢性变应性气道疾病小鼠模型诱导炎症和重塑,以确定体内对甲胆碱的高反应性是否与体外气管和小气道的反应性一致。Balb/C小鼠致敏(第0、14天),卵清蛋白攻毒(3次/周,6周)。气道反应性在体内与盐刺激对照组进行比较,评估全肺阻力,并在体外测量气管收缩力和肺切片内小气道狭窄的幅度/速率。过敏原刺激后气道炎症、上皮重塑和纤维化明显增加。体内对甲胆碱的高反应在离体气管中维持。相反,与对照组相比,甲胆碱诱导的狭窄速度较慢,在小气道中的效力降低。IL-1/ tnf - α体外孵育不改变反应性。考虑到在体内和体外气管制剂中对同一激动剂的高反应性,慢性卵清蛋白攻击后肺切片内小气道对甲胆碱的低反应性是出乎意料的。这一发现可能反映了过敏原攻击后小气道与周围实质组织相互作用的改变,以反对气道狭窄和关闭。
The relative contributions of large and small airways to hyperresponsiveness in asthma have yet to be fully assessed. This study used a mouse model of chronic allergic airways disease to induce inflammation and remodelling and determine whether in vivo hyperresponsiveness to methacholine is consistent with in vitro reactivity of trachea and small airways. Balb/C mice were sensitised (days 0, 14) and challenged (3 times/week, 6 weeks) with ovalbumin. Airway reactivity was compared with saline-challenged controls in vivo assessing whole lung resistance, and in vitro measuring the force of tracheal contraction and the magnitude/rate of small airway narrowing within lung slices. Increased airway inflammation, epithelial remodelling and fibrosis were evident following allergen challenge. In vivo hyperresponsiveness to methacholine was maintained in isolated trachea. In contrast, methacholine induced slower narrowing, with reduced potency in small airways compared to controls. In vitro incubation with IL-1/TNFα did not alter reactivity. The hyporesponsiveness to methacholine in small airways within lung slices following chronic ovalbumin challenge was unexpected, given hyperresponsiveness to the same agonist both in vivo and in vitro in tracheal preparations. This finding may reflect the altered interactions of small airways with surrounding parenchymal tissue after allergen challenge to oppose airway narrowing and closure.
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