Human adenovirus modulates surfactant phospholipid trafficking.
Human adenovirus modulates surfactant phospholipid trafficking.
复制标题
人腺病毒调节表面活性剂磷脂运输。
DOI：
10.1111/j.1600-0854.2007.00641.x
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Mallampalli,RamaK
中科院分区：
文献类型：
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作者：
Miakotina,OlgaL;McCoy,DiannM;Shi,Lei;Look,DwightC;Mallampalli,RamaK
富含磷脂酰胆碱（PC）的表面活性剂通过经典的心尖分泌途径分泌到空气空间中，从而维持肺的稳定性。在此，我们发现腺病毒感染通过抑制其顶端分泌并通过基底外侧途径重定向其在肺泡细胞中的输出来减少肺中的表面活性剂PC。复制缺陷型腺病毒 (Ad) 没有观察到这些效应，特别是缺乏早期区域 1 (E1) 基因产物。在药物抑制 ATP 结合盒蛋白后、将小干扰 RNA 引入脂质泵 ATP 结合盒转运蛋白 A1 (ABCA1) 或在 ABCA1 缺陷的人丹吉尔病成纤维细胞中后，未观察到腺病毒对细胞基底外侧 PC 输出的刺激。腺病毒及其E1A基因产物通过转录激活ABCA1基因来增加ABCA1水平。因此，Ad 部分地通过触发 ABCA1 定向的基底外侧 PC 输出来降低表面活性剂，从而限制了用于顶端分泌的表面活性剂 PC 的细胞池。结果支持了一种新的途径，即病毒病原体破坏表面活性剂的运输。
Surfactant, highly enriched with phosphatidylcholine (PC), is secreted into the airspace by a classic apical secretory route, thereby maintaining lung stability. Herein, we show that adenoviral infection decreases surfactant PC in lungs by inhibiting its apical secretion and redirecting its export in alveolar cells by a basolateral route. These effects were not observed with replication‐deficient adenovirus (Ad), specifically lacking early region 1 (E1) gene products. Adenoviral stimulation of basolateral PC export from cells was not observed after pharmacologic inhibition of ATP‐binding cassette proteins, after introduction of small interfering RNA to the lipid pump ATP‐binding cassette transporter A1 (ABCA1) or in ABCA1‐defective human Tangier disease fibroblasts. Adenovirus and itsE1Agene product increased ABCA1 levels by transcriptionally activating the ABCA1 gene. Thus, Ad lowers surfactant, in part, by triggering ABCA1‐directed basolateral PC export, thereby limiting the cellular pool of surfactant PC destined for apical secretion. The results support a novel pathway, whereby a viral pathogen disrupts surfactant trafficking.