Chua Felix, Laurent Geoffrey J
Centre for Respiratory Research, Royal Free and University College London Medical School, Rayne Building, 5 University Street, London WC1E 6JJ, UK.
Proc Am Thorac Soc. 2006 Jul;3(5):424-7. doi: 10.1513/pats.200603-078AW.
Of the myriad proteolytic enzymes implicated in the development of lung disease, neutrophil elastase has undoubtedly some of the most versatile effects. Although its key physiologic role is in innate host defense, it can also participate in tissue remodeling and possesses secretagogue actions that are now recognized as important to local inflammatory responses. Although unopposed neutrophil elastase activity has been implicated in the development of emphysema for several decades, only relatively recently has a pathogenetic function been ascribed to this serine proteinase in situations where excessive extracellular matrix deposition occurs. The use of genetically manipulated animal models is starting to uncover the potential ways in which its actions might influence fibrotic lung repair. Emerging evidence suggests that the engagement of cellular pathways with more direct effects on fibrogenic mediator generation and collagen synthesis appears to underpin the actions of neutrophil elastase in promoting lung matrix accumulation.
在与肺部疾病发展相关的众多蛋白水解酶中，中性粒细胞弹性蛋白酶无疑具有一些最为多样的作用。尽管其关键的生理作用在于先天性宿主防御，但它也能参与组织重塑，并具有促分泌作用，现在人们认识到这些作用对局部炎症反应很重要。尽管几十年来一直认为不受抑制的中性粒细胞弹性蛋白酶活性与肺气肿的发展有关，但直到最近才将这种丝氨酸蛋白酶的致病功能归因于细胞外基质过度沉积的情况。使用基因操纵动物模型开始揭示其作用可能影响肺纤维化修复的潜在方式。新出现的证据表明，与对纤维生成介质生成和胶原蛋白合成有更直接影响的细胞途径的参与似乎是中性粒细胞弹性蛋白酶促进肺基质积累作用的基础。
