哮喘联盟

   摘要
   人类的气道长期与环境中的病原体相关分子以及危险相关分子接触。哮喘患者的气道可能较正常人对这些分子更加敏感从而导致炎症复合物的激活。但是炎症复合物的激活在哮喘疾病进展及恶化过程中所发挥的作用目前仍研究得不够透彻，并且存在很多争议。哮喘患者是一类由于不同炎症反应模式及不同免疫机制导致的异质性很大的患者群体。其中一种发病机制是由于炎症复合物的激活使白介素（IL）1β/IL-18的分泌增加、辅助T细胞－17活化和IL-8/IL-6过量产生，从而进一步促进中性粒细胞性炎症的发生而导致的。炎症复合物激活在哮喘实验动物模型中被认为在疾病的进展过程中发挥着重要的作用，而且目前也有研究表明在中性粒细胞炎症性哮喘患者气道中存在炎症复合物激活的现象。除了caspase-1的激活，蛋白酶3以及其它来自活化中性粒细胞的蛋白酶可直接裂解IL-1β和IL-18前体使其活化成IL-1β和IL-18，从而在不激活炎症复合物的情况下进一步导致后续适应性免疫反应的发生。目前有研究表明，哮喘患者气道中的中性粒细胞可能同时具有激活炎症复合物以及放大免疫应答的作用。在所有中性粒细胞分泌的炎症介质中，S100A9可能与炎症复合物协同作用并放大气道炎症反应的炎症介质之一。
 

（苏楠 审校）
Asia Pac Allergy. 2014 Oct;4(4):187-96. doi: 10.5415/apallergy.2014.4.4.187. Epub 2014 Oct 29.


 

Role of inflammasome activation in development and exacerbation of asthma.
 

Lee TH1, Song HJ1, Park CS2.
 

ABSTRACT
Human airways contact with pathogen-associated molecular patterns and danger-associated molecular patterns present in many environments. Asthmatic's airways may be more susceptible to these patterns and lead to inflammasome activation; however, the participation of inflammasome in the development and exacerbation of asthma is not fully understood and remains controversial. Asthma is a heterogeneous group composed of different airway inflammation patterns with different underlying immune mechanisms. One mechanism is neutrophilic airway inflammation based on the axis of inflammasome activation, interleukin (IL) 1β/IL-18 production, T helper 17 activation, IL-8/IL-6 overproduction, and neutrophilic inflammation. The role of inflammasome activation has been highlighted in experimental asthma models and some evidence of inflammasome activation has been recently demonstrated in human neutrophilic asthmatic airways. In addition to caspase-1 activation, proteinase 3 and other protease from activated neutrophils directly cleave pro-IL-1β and pro-IL-18 to IL-1β and IL-18, which contribute to the phenotype of subsequent adaptive immune responses without inflammasome activation. Data suggests that neutrophilics in asthmatic airways may have an additional effect in initiating inflammasome activation and amplifying immune responses. Among the mediators from neutrophils, S100A9 seems to be one candidate mediator to explain the action of neutrophils in amplifying the airway inflammation in concert with inflammasome.
 

Asia Pac Allergy. 2014 Oct;4(4):187-96. doi: 10.5415/apallergy.2014.4.4.187. Epub 2014 Oct 29.