Prenatal cigarette smoke decreases lung cAMP and increases airway hyperresponsiveness
Prenatal cigarette smoke decreases lung cAMP and increases airway hyperresponsiveness
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DOI：
10.1164/rccm.200211-1262oc
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发表时间：
2003-08-01
影响因子：
24.7
通讯作者：
Sopori, ML
中科院分区：
文献类型：
--
作者：
Singh, SP;Barrett, EG;Sopori, ML
流行病学研究表明，在子宫内暴露于烟草烟雾，主要是通过母亲吸烟，增加儿童哮喘的风险;然而，这种现象的机制尚不清楚。环磷酸腺苷能松弛肺内的气道平滑肌，并起到平喘作用。在这项研究中，我们研究了子宫内香烟烟雾暴露的Balb/c小鼠气道反应性的影响，通过Penh测量。出生前暴露于香烟烟雾而出生后未暴露于香烟烟雾的动物在单次气管内注射烟曲霉提取物后表现出气道高反应性增加。气道高反应性增加与肺中白细胞迁移或粘液产生增加无关，但与肺环磷酸腺苷水平降低、磷酸二酯酶-4酶活性增加和磷酸二酯酶-4D（PDE 4D）亚型特异性信使核糖核酸在肺中的表达有因果关系。成年小鼠暴露于香烟烟雾中不会显著改变气道反应性、环磷酸腺苷水平或磷酸二酯酶活性。这些结果表明，产前暴露于香烟烟雾影响肺气道反应性，通过调节肺环磷酸腺苷水平，通过磷酸二酯酶-4D活性的变化，这些影响是独立的显着粘液生产或白细胞招募到肺。
Epidemiologic studies suggest that in utero exposure to tobacco smoke, primarily through maternal smoking, increases the risk for asthma in children; however, the mechanism of this phenomenon is not clear. Cyclic adenosine monophosphate relaxes airway smooth muscles in the lung and acts as an antiasthmatic. In this study, we examined the effects of in utero cigarette smoke exposure of Balb/c mice on airway responsiveness, as determined by Penh measurements. Animals exposed prenatally but not postnatally to cigarette smoke exhibited increased airway hyperresponsiveness after a single intratracheal injection of Aspergillus fumigatus extract. The increased airway hyperresponsiveness was not associated with increased leukocyte migration or mucous production in the lung but was causally related to decreased lung cyclic adenosine monophosphate levels, increased phosphodlesterase-4 enzymatic activity, and phosphodiesterase-4D (PDE4D) isoform-specific messenger ribonucleic acid expression in the lung. Exposure of adult mice to cigarette smoke did not significantly alter airway responsiveness, cyclic adenosine monophosphate levels, or the phosphodiesterase activity. These results suggest that prenatal exposure to cigarette smoke affects lung airway reactivity by modulating the lung cyclic adenosine monophosphate levels through changes in phosphodiesterase-4D activity, and these effects are independent of significant mucous production or leukocyte recruitment into the lung.