Nerve growth factor and nerve growth factor receptors in respiratory syncytial virus-infected lungs

Nerve growth factor and nerve growth factor receptors in respiratory syncytial virus-infected lungs
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DOI:
10.1152/ajplung.00414.2001
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发表时间:
2002-08-01
影响因子:
4.9
通讯作者:
Piedimonte, G
Piedimonte, G
中科院分区:
医学2区
文献类型:
--
作者:
Hu, CP;Wedde-Beer, K;Piedimonte, G

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神经生长因子(NGF)控制感觉神经的发育和反应,并调节免疫炎症反应。呼吸道合胞病毒(RSV)通过上调P物质受体神经激肽1(NK1)的表达,增强大鼠呼吸道感觉神经的促炎效应。我们研究了NGF及其TrkA和p75受体在肺中的表达是否与年龄有关,在RSV感染期间是否上调,以及它是否影响神经源性炎症。在断奶后2~12周龄处死无病原体大鼠,并分别接种RSV或无病毒培养液。在无病原体感染的大鼠中,NGF及其受体的表达随着年龄的增长而下降,而在断奶和成年大鼠中,RSV使NGF、TrkA和p75的表达增加了一倍。外源性NGF上调肺组织中NK1受体的表达。抗NGF抗体可抑制RSV感染肺中NK1受体的上调和神经源性炎症。这些数据表明,肺中NGF及其受体的表达随着年龄的增长而生理性地下降,但被RSV上调,是神经源性炎症的主要决定因素。
Nerve growth factor (NGF) controls sensorineural development and responsiveness and modulates immunoinflammatory reactions. Respiratory syncytial virus (RSV) potentiates the proinflammatory effects of sensory nerves in rat airways by upregulating the substance P receptor, neurokinin 1 (NK1). We investigated whether the expression of NGF and its trkA and p75 receptors in the lungs is age dependent, whether it is upregulated during RSV infection, and whether it affects neurogenic inflammation. Pathogen-free rats were killed at 2 (weanling) to 12 (adult) wk of age; in addition, subgroups of rats were inoculated with RSV or virus-free medium. In pathogen-free rats, expression of NGF and its receptors in the lungs declined with age, but RSV doubled expression of NGF, trkA, and p75 in weanling and adult rats. Exogenous NGF upregulated NK1 receptor expression in the lungs. Anti-NGF antibody inhibited NK1 receptor upregulation and neurogenic inflammation in RSV-infected lungs. These data indicate that expression of NGF and its receptors in the lungs declines physiologically with age but is upregulated by RSV and is a major determinant of neurogenic inflammation.