Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia
Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia
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DOI：
10.1016/j.alcohol.2007.07.006
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发表时间：
2007-08-01
期刊：
影响因子：
2.3
通讯作者：
Ackermann, Mark R.
中科院分区：
文献类型：
--
作者：
Lazic, Tatjana;Wyatt, Todd A.;Ackermann, Mark R.
除了对神经发育的影响外，怀孕期间大量饮酒还与免疫调节和早产有关。反过来，早产又与呼吸道合胞病毒 (RSV) 等各种传染源的易感性增加有关。肺部先天防御的第一道防线包括粘液纤毛装置，它可以排出气道分泌物中截留的微生物。表面活性蛋白 A 和 D（分别为 SP-A 和 SP-D）是肺部先天免疫的附加成分，在肺部防御吸入病原体中发挥着重要作用。本研究的目的是确定妊娠晚期长期饮酒是否会改变粘膜纤毛器的功能以及胎儿肺上皮细胞 SP-A 和 SP-D 的表达。十六只已交配的母羊被分配到两个不同的组；乙醇暴露组中的母羊在妊娠晚期通过手术植入皱胃内插管接受乙醇，对照组中母羊接受等量的水而不是乙醇。在这两组中，母羊被进一步随机分配到足月组（其中羔羊自然分娩）和早产组（其中羔羊通过腹部切口和子宫切开术过早分娩）。每周以 1 g/kg 体重的 40% 溶液形式施用 5 次乙醇。给药后 6 小时测量的平均母体血清酒精浓度为 16.3 +/- 4.36 mg/dl。收集六只足月羔羊的气管来评估纤毛跳动频率（CBF）。收集所有 (24) 只羔羊的肺组织，用于 SP-A 和 SP-D 蛋白产生的免疫组织化学分析以及 SP-A 和 SP-D mRNA 水平的荧光实时定量聚合酶链反应分析。怀孕期间接触乙醇通过乙醇介导的 cAMP 依赖性蛋白激酶脱敏作用显着阻止了 CBF 的刺激增加。此外，与早产/对照组相比，早产/乙醇暴露组羔羊的 SP-A mRNA 表达显着降低 (P =.004)； SP-D 没有发现显着变化。足月/暴露于乙醇的羔羊的 mRNA 水平没有显着变化，但与足月/对照羔羊相比，可检测到的 SP-A 蛋白显着减少 (P =.02)。这些发现表明，妊娠晚期母亲长期摄入乙醇会改变胎儿肺部的先天免疫基因表达。这些改变可能是早产儿在子宫内接触乙醇、RSV 和其他微生物制剂的易感性增加的基础。 (C) 2007 Elsevier Inc. 保留所有权利。
In addition to neurodevelopmental effects, alcohol consumption at high levels during pregnancy is associated with immunomodulation and premature birth. Premature birth, in turn, is associated with increased susceptibility to various infectious agents such as respiratory syncytial virus (RSV). The initial line of pulmonary innate defense includes the mucociliary apparatus, which expels microorganisms trapped within the airway secretions. Surfactant proteins A and D (SP-A and SP-D, respectively) are additional components of pulmonary innate immunity and have an important role in pulmonary defense against inhaled pathogens. The purpose of this study was to determine if chronic alcohol consumption during the third trimester of pregnancy alters the function of the mucociliary apparatus and expression of SP-A and SP-D of fetal lung epithelia. Sixteen, date-mated ewes were assigned to two different groups; an ethanol-exposed group in which ewes received ethanol through surgically implanted intra-abomasal cannula during the third trimester of pregnancy, and a control group in which ewes received the equivalent amount of water instead of ethanol. Within these two groups, ewes were further randomly assigned to a fullterm group in which the lambs were naturally delivered, and a preterm group in which the lambs were delivered prematurely via an abdominal incision and uterotomy. Ethanol was administered five times a week as a 40% solution at 1 g/kg of body weight. The mean maternal serum alcohol concentration measured 6 h postadministration was 16.3 +/- 4.36 mg/dl. Tracheas from six full-term lambs were collected to assess ciliary beat frequency (CBF). The lung tissue from all (24) lambs was collected for immunohistochemistry analysis of SP-A and SP-D protein production and fluorogenic real-time quantitative polymerase chain reaction analysis of SP-A and SP-D mRNA levels. Exposure to ethanol during pregnancy significantly blocked stimulated increase in CBF through ethanol-mediated desensitization of cAMP-dependent protein kinase. In addition, preterm born/ethanol-exposed lambs showed significantly decreased SP-A mRNA expression when compared with the preterm born/control group (P =.004); no significant changes were seen with SP-D. The full-term/ethanol-exposed lambs had no significant alterations in mRNA levels, but had significantly less detectable SP-A protein when compared with the full-term/ control lambs (P =.02). These findings suggest that chronic maternal ethanol consumption during the third trimester of pregnancy alters innate immune gene expression in fetal lung. These alterations may underlie increased susceptibility of preterm infants, exposed to ethanol in utero, to RSV and other microbial agents. (C) 2007 Elsevier Inc. All rights reserved.