Airway Smooth Muscle Sensitivity to Methacholine in Precision-Cut Lung Slices (PCLS) from Ovalbumin-induced Asthmatic Mice.
Airway Smooth Muscle Sensitivity to Methacholine in Precision-Cut Lung Slices (PCLS) from Ovalbumin-induced Asthmatic Mice.
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DOI：
10.4196/kjpp.2015.19.1.65
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Kim SJ
中科院分区：
文献类型：
--
作者：
Kim HJ;Kim Y;Park SJ;Bae B;Kang HR;Cho SH;Yoo HY;Nam JH;Kim WK;Kim SJ
哮喘是一种以气道高反应性（AHR）和可逆性气道阻塞为特征的慢性炎症性疾病。乙酰甲胆碱（Methacholine，MCh）被广泛应用于支气管激发试验，以评价气道阻力。在实验研究中，卵清蛋白诱导的致敏作用经常用于啮齿动物（卵蛋白哮喘）。然而，尽管炎症组织学和AHR在体内，它仍然不清楚是否从Ova-哮喘的气道平滑肌分离的MCh敏感性持续改变。在这项研究中，通过分析气道腔空间（AW），比较了来自对照、Ova哮喘和IL-13过表达转基因小鼠（IL-13 TG）的精密切割肺切片（PCLS）中气道的收缩。用体积描记器测量在体气道阻力。在Ova-哮喘和IL-13 TG小鼠中证实了AHR和BAL液中炎性细胞增加。在所有三组的PCLS中，观察到MCh浓度依赖性气道管腔狭窄（ΔAW）。与体内AHR相比，MCh对OVA哮喘ΔAW和IL-13 TG的EC 50与对照组无差异，表明对MCh的敏感性不变。尽管在卵型哮喘中，在MCH洗脱后AW恢复显示缓慢趋势，但这种变化也无统计学意义。IL-13 TG组60 mM K+诱导的ΔAW（60 K收缩）大于对照组，而Ova哮喘组的60 K收缩不受影响。此外，Ova-哮喘组的ΔAW明显小于对照组和IL-13 TG组。总之，卵母细胞哮喘和IL-13 TG中的AHR未反映在来自PCLS的分离气道的收缩性中。模型动物的AHR似乎需要在组织制备期间可清洗的内在激动剂或炎症微环境。
Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR) and reversible airway obstruction. Methacholine (MCh) is widely used in broncho-provocation test to evaluate airway resistance. For experimental investigation, ovalbumin-induced sensitization is frequently used in rodents (Ova-asthma). However, albeit the inflammatory histology and AHR in vivo, it remains unclear whether the MCh sensitivity of airway smooth muscle isolated from Ova-asthma is persistently changed. In this study, the contractions of airways in precision-cut lung slices (PCLS) from control, Ova-asthma, and IL-13 overexpressed transgenic mice (IL-13TG) were compared by analyzing the airway lumen space (AW). The airway resistance in vivo was measured using plethysmograph. AHR and increased inflammatory cells in BAL fluid were confirmed in Ova-asthma and IL-13TG mice. In the PCLS from all three groups, MCh concentration-dependent narrowing of airway lumen (ΔAW) was observed. In contrast to the AHR in vivo, the EC50 of MCh for ΔAW from Ova-asthma and IL-13TG were not different from control, indicating unchanged sensitivity to MCh. Although the AW recovery upon MCh-washout showed sluggish tendency in Ova-asthma, the change was also statistically insignificant. Membrane depolarization-induced ΔAW by 60 mM K+ (60K-contraction) was larger in IL-13TG than control, whereas 60K-contraction of Ova-asthma was unaffected. Furthermore, serotonin-induced ΔAW of Ova-asthma was smaller than control and IL-13TG. Taken together, the AHR in Ova-asthma and IL-13TG are not reflected in the contractility of isolated airways from PCLS. The AHR of the model animals seems to require intrinsic agonists or inflammatory microenvironment that is washable during tissue preparation.
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DOI：
10.1164/ajrccm.156.3.9606031
发表时间：
1997-09-01
影响因子：
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作者：
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影响因子：
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