Neurotrophin overexpression in lower airways of infants with respiratory syncytial virus infection
Neurotrophin overexpression in lower airways of infants with respiratory syncytial virus infection
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DOI：
10.1164/rccm.200412-1693oc
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发表时间：
2005-07-15
影响因子：
24.7
通讯作者：
Piedimonte, G
中科院分区：
文献类型：
--
作者：
Tortorolo, L;Langer, A;Piedimonte, G
基本原理：神经生长因子及其受体在由呼吸道合胞病毒（RSV）引起的下呼吸道感染的断奶大鼠的肺中上调，这是针对病毒的炎症反应的主要机制。然而，在人类中没有可用的信息。目的：我们试图确定在RSV感染的人类婴儿中神经营养因子和受体的表达是否增加。研究方法：我们使用了一种高度敏感的免疫测定法来测量血清样本中神经生长因子和脑源性神经营养因子蛋白的浓度，以及非支气管镜支气管肺泡灌洗液的上清液和细胞组分中的浓度。我们还使用免疫荧光法检测气道细胞中酪氨酸激酶受体TrkA的表达，该受体以高亲和力结合神经生长因子。在插管后24和48小时从31名机械通气婴儿中采集样本：15名RSV感染患者，5名呼吸道感染患者RSV阴性，11名术后患者无呼吸道感染。主要结果：数据显示，与对照婴儿相比，从RSV感染婴儿获得的支气管肺泡灌洗样品的细胞组分中两种神经营养因子的浓度显著更高，而在上清液或血清样品中未发现显著差异。我们还检测到酪氨酸激酶受体免疫反应性仅在细胞从呼吸道感染RSV。结论：我们的结论是，神经营养因子和受体在呼吸道合胞病毒感染的人气道中过表达，并可能有助于气道炎症和过敏反应。
Rationale: Nerve growth factor and its receptors are upregulated in the lungs of weanling rats with lower respiratory tract infection caused by the respiratory syncytial virus (RSV), and this is a major mechanism of the inflammatory response against the virus. However, no information is available in humans. Objectives: We sought to determine whether the expression of neurotrophic factors and receptors is increased in human infants infected with RSV. Methods: We used a highly sensitive immunoassay to measure the concentrations of nerve growth factor and brain-derived neurotrophic factor proteins in serum samples and in the supernatants and cell fractions of nonbronchoscopic bronchoalveolar lavage fluid. We also used immunofluorescence to detect expression in airway cells of the tyrosine kinase receptor TrkA, which binds nerve growth factor with high affinity. Samples were obtained at 24 and 48 hours postintubation from 31 mechanically ventilated infants: 15 patients with RSV infection, 5 patients with respiratory infection negative for RSV, and I I postsurgical patients without respiratory infection. Main Results: Data show significantly higher concentrations of both neurotrophins in the cell fractions of bronchoalveolar lavage samples obtained from infants with RSV infection compared with control infants, whereas no significant difference was found in supernatants or serum samples. We also detected tyrosine kinase receptor immunoreactivity only in cells from airways infected with RSV. Conclusions: We conclude that neurotrophic factors and receptors are overexpressed in human airways infected by RSV, and may contribute to airway inflammation and hype rreactivity.