Neutrophil elastase: mediator of extracellular matrix destruction and accumulation

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.