Samarasinghe Amali E, Hoselton Scott A, Schuh Jane M
Department of Veterinary and Microbiological Sciences, North Dakota State University, P.O. Box 6050, Fargo ND 58108-6050, USA.
Regul Pept. 2010 Sep 24;164(2-3):151-7. doi: 10.1016/j.regpep.2010.05.017. Epub 2010 Jun 8.
Vasoactive intestinal peptide (VIP) is a neuropeptide with cytokine properties that is abundant in the lung. VIP null mice exhibit spontaneous airway inflammation and hyperresponsiveness emphasizing VIP's "anti-asthma" potential. Although VIP's impending protective role in the lung has been demonstrated, its localization in the naïve and allergic murine lungs has not. To this aim, we analyzed the availability of VIP and its protease, neutral peptidase (NEP), in naïve and Aspergillus-sensitized and challenged murine lungs after 3, 7, and 14days. Both VIP and NEP were predominantly localized to the columnar epithelia of the airways in naïve lungs. A marked decrease in VIP occurred in these cells 3days after allergen challenge. NEP localization in the columnar epithelia decreased after allergen challenge. At day 14, VIP localization in the columnar epithelia and arteriolar smooth muscle increased while NEP localization at these sites remained low. This study provides new insights into the local regulation of VIP in the columnar epithelia of the allergic lung. Its altered availability in the context of allergy provides fresh evidence for the modulation of pulmonary inflammation by VIP.
血管活性肠肽(VIP)是一种具有细胞因子特性的神经肽,在肺中含量丰富。VIP基因敲除小鼠表现出自发性气道炎症和高反应性,这突出了VIP的“抗哮喘”潜力。尽管已经证明了VIP在肺中的潜在保护作用,但其在未致敏和过敏性小鼠肺中的定位尚未明确。为此,我们分析了在3天、7天和14天后,未致敏以及经曲霉菌致敏和激发的小鼠肺中VIP及其蛋白酶中性肽酶(NEP)的情况。在未致敏的肺中,VIP和NEP主要定位于气道的柱状上皮细胞。过敏原激发3天后,这些细胞中的VIP显著减少。过敏原激发后,柱状上皮细胞中的NEP定位减少。在第14天,柱状上皮细胞和小动脉平滑肌中的VIP定位增加,而这些部位的NEP定位仍然较低。这项研究为过敏性肺柱状上皮细胞中VIP的局部调节提供了新的见解。其在过敏情况下可用性的改变为VIP调节肺部炎症提供了新的证据。