Neutrophil serine proteases (NSPs)

Neutrophil serine proteases (NSPs), primarily comprising neutrophil elastase (NE), cathepsin G (CG), and proteinase 3 (PR3), are a group of potent proteolytic enzymes stored in the azurophilic granules of neutrophils [1]. These enzymes are essential for the innate immune response, where they facilitate the degradation of engulfed pathogens and enable neutrophil migration by cleaving extracellular matrix components like elastin and collagen [2]. Under healthy conditions, NSP activity is strictly regulated by endogenous inhibitors such as alpha-1 antitrypsin (A1AT) [3]. However, an imbalance between these proteases and their inhibitors—often due to chronic inflammation or genetic factors—leads to excessive tissue damage, particularly in the lungs [4]. This pathological process is central to the development of chronic obstructive pulmonary disease (COPD), cystic fibrosis, and bronchiectasis [5]. Therapeutic strategies include the development of small-molecule inhibitors like sivelestat and alvelestat, as well as the use of A1AT replacement therapy to restore the protease-antiprotease balance [6]. Additionally, targeting dipeptidyl peptidase 1 (DPP1) has emerged as a method to prevent the activation of these proteases during neutrophil maturation [7].

Other names

Elastase and other neutral proteasesNeutrophil elastaseCathepsin GProteinase 3Azurophil granule proteasesNeutral serine proteases

Direct inhibition of serine protease catalytic activity or inhibition of dipeptidyl peptidase 1 (DPP1) to prevent protease activation during neutrophil maturation.