Stress induces substance P in vagal sensory neurons innervating the mouse airways
Stress induces substance P in vagal sensory neurons innervating the mouse airways
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DOI：
10.1111/j.1365-2222.2006.02533.x
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发表时间：
2006-08-01
影响因子：
6.1
通讯作者：
Dinh, Q. T.
中科院分区：
文献类型：
--
作者：
Joachim, R. A.;Cifuentes, L. B.;Dinh, Q. T.
速激素样物质P （SP）已被证明在引发和持续气道炎症中起重要作用。此外，它们应该被释放到组织中以应对压力。目的探讨应激单独或联合变应性气道炎症对小鼠气道感觉神经元SP表达的影响。方法对Balb/c小鼠进行卵白蛋白（OVA）致敏，然后进行致敏气溶胶暴露，并与非致敏对照组进行比较。此外，ova致敏小鼠、ova致敏小鼠和未致敏小鼠暴露于声应激。应用逆行示踪结合免疫组织化学方法分析了SP在颈节和结节神经节复合体气道特异性和整体迷走感觉神经元中的表达。实时荧光定量PCR检测肺组织中SP前体pre - protachykinin A (PPT-A) mRNA的表达。取支气管肺泡灌洗液，测定细胞数量和分化情况。结果与对照组相比，应激和/或过敏性气道炎症显著增加小鼠下气道逆行标记迷走感觉神经元中SP的表达[应激：15.7 +/- 0.8%（逆行标记神经元百分比，平均+/- SEM）；过敏原：17.9±0.4%；过敏原/压力:13.1 + / - 0.7%与控制:6.3 + / - 0.3%)。同样，通过神经元标记蛋白基因产物（PGP）鉴定的迷走感觉神经元中SP的表达增加9.5[应激：9.3 +/- 0.6% (PGP 9.5阳性神经元的百分比，平均+/- SEM)；过敏原：12.5 +/- 0.4%；过敏原/压力:10.2 + / - 0.4%与控制:5.1 + / - 0.3%)。此外，应激显著增加ova致敏和攻击动物肺组织中PPT-A mRNA的表达，免疫组织化学鉴定免疫细胞是肺中SP的额外来源。与神经元SP表达增强相关的是，暴露于过敏原后，BAL中白细胞数量显著增加。此外，应激显著增加了过敏原诱导的气道炎症，这可以通过BAL液中白细胞数量的增加来确定。结论声应激的中枢事件可刺激气道特异性神经元的SP表达。然而，在致敏应激小鼠中，额外的局部SP来源（可能是炎症细胞）可能会增强过敏性气道炎症。
Background Tachykinins-like substance P (SP) have been shown to play an important role in initiating and perpetuating airway inflammation. Furthermore, they are supposed to be released into tissues in response to stress.Objective The aim of this study was to investigate the effects of stress alone or in combination with allergic airway inflammation on SP expression in sensory neurons innervating the mouse airways.Methods Balb/c mice were systemically sensitized to ovalbumin (OVA), followed by allergen aerosol exposure, and compared with non-sensitized controls. Additionally, OVA-sensitized and -challenged and non-sensitized mice were exposed to sound stress. SP expression in airway-specific and overall vagal sensory neurons of the jugular and nodose ganglion complex was analysed using retrograde neuronal tracing in combination with immunohistochemistry. Preprotachykinin A (PPT-A) mRNA, the precursor for SP, was quantified in lung tissue by real-time PCR. Bronchoalveolar lavage (BAL) fluid was obtained, and cell numbers and differentiation were determined.Results Stress and/or allergic airway inflammation significantly increased SP expression in retrograde-labelled vagal sensory neurons from the mouse lower airways compared with controls [stress: 15.7 +/- 0.8% (% of retrograde-labelled neurons, mean +/- SEM); allergen: 17.9 +/- 0.4%; allergen/stress: 13.1 +/- 0.7% vs. controls: 6.3 +/- 0.3%]. Similarly, SP expression increased in overall vagal sensory neurons identified by the neuronal marker protein gene product (PGP) 9.5 [stress: 9.3 +/- 0.6% (% of PGP 9.5-positive neurons, means +/- SEM); allergen: 12.5 +/- 0.4%; allergen/stress: 10.2 +/- 0.4% vs. controls: 5.1 +/- 0.3%]. Furthermore, stress significantly increased PPT-A mRNA expression in lung tissue from OVA-sensitized and -challenged animals, and immune cells were identified as an additional source of SP in the lung by immunohistochemistry. Associated with enhanced neuronal SP expression, a significantly higher number of leucocytes were found in the BAL following allergen exposure. Further, stress significantly increased allergen-induced airway inflammation identified by increased leucocyte numbers in BAL fluids.Conclusion The central event of sound stress leads to the stimulation of SP expression in airway-specific neurons. However, in sensitized stressed mice an additional local source of SP (probably inflammatory cells) might enhance allergic airway inflammation.