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美国霍华德?休斯医学研究所的研究人员对一个哮喘的小鼠模型的一项研究表明，肺的感觉神经元是急性哮喘发作典型的气道收缩的关键调控因素，这提示需要开发针对神经系统而非仅仅针对免疫系统的哮喘疗法。 |
美国霍华德?休斯医学研究所的研究人员对一个哮喘的小鼠模型的一项研究表明，肺的感觉神经元是急性哮喘发作典型的气道收缩的关键调控因素，这提示需要开发针对神经系统而非仅仅针对免疫系统的哮喘疗法。相关文章发表于2014年7月21日的《PNAS》杂志上。
患哮喘的人们面对粘液制造过多造成的慢性肺阻塞以及过敏原可能导致气道收缩的急性发作的折磨。由于免疫系统对过敏原做出应答而导致的几种症状通过免疫抑制仅能得到部分缓解。
为了研究神经系统的这种部分作用，Dimitri Tr?nkner、Charles Zuker以及同事研究了卵清蛋白导致急性哮喘发作模型的小鼠肺的感觉神经元，卵清蛋白是见于鸡蛋蛋白的一种过敏原。这组作者用化学方法让位于迷走神经的神经节上的肺感觉神经元的不同群体失去活性，然后观察哮喘症状的变化。
让其中一个群体失去活性导致了通常会由接触卵清蛋白诱导产生的气道反应过度和收缩的消失，但是没有改变这种免疫应答。此外，刺激同一组神经元让气道反应过度加剧。这组作者说，哮喘的气道反应过度可能受到了不同于免疫系统造成的症状的神经系统的控制，这提示了哮喘治疗的另一个可能的途径。(来源：生物帮)
原文摘要：
Population of sensory neurons essential for asthmatichyperreactivity of inflamed airways
Dimitri Tr?nkner, Nadeau Hahne, Ken Sugino, Mark A. Hoon and Charles Zuker
Asthma is a common debilitating inflammatory lung disease affecting over 200 million people worldwide. Here, we investigated neurogenic components involved in asthmatic-like attacks using the ovalbumin-sensitized murine model of the disease, and identified a specific population of neurons that are requiredfor airway hyperreactivity. We show that ablating or genetically silencing these neurons abolished the hyperreactive broncho-constrictions, even in the presence of a fully developed lung inflammatory immune response. These neurons are found in the vagal ganglia and are characterized by the expression of the transient receptor potential vanilloid 1 (TRPV1) ion channel. However, the TRPV1 channel itself is not required for the asthmatic-like hyperreactive airway response. We also demonstrate that optoGENEtic stimulation of this population of TRP-expressing cells with channelrhodopsin dramatically exacerbates airway hyperreactivity of inflamed airways. Notably, these cells express the sphingosine-1-phosphate receptor 3 (S1PR3), and stimulation with a S1PR3 agonist efficiently induced broncho-constrictions, even in the absence of ovalbumin sensitization and inflammation. Our results show that the airway hyperreactivityphenotype can be physiologically dissociated from the immune component, and provide a platform fordevising therapeutic approaches to asthma that target these pathways separately.