Neutrophil serine protease (NSP)

Neutrophil serine proteases (NSPs) are a group of specialized enzymes, including neutrophil elastase, proteinase 3, cathepsin G, and NSP4, stored within the azurophilic granules of neutrophils. They play a fundamental role in the innate immune system by degrading engulfed pathogens within phagolysosomes and contributing to the formation of neutrophil extracellular traps (NETs). However, when released excessively into the extracellular space, NSPs can cause significant tissue damage by degrading structural proteins like elastin and collagen and by activating pro-inflammatory cytokines. This dysregulation is a primary driver of chronic inflammatory lung diseases such as bronchiectasis and chronic obstructive pulmonary disease (COPD). Therapeutic strategies targeting NSPs include direct inhibitors of individual enzymes or the inhibition of dipeptidyl peptidase 1 (DPP1), the master enzyme responsible for activating all NSPs during neutrophil development.

Other names

Neutrophil-derived serine proteasesPolymorphonuclear leukocyte serine proteasesNeutrophil elastase-like serine proteases

Inhibition of the enzymatic activity of mature proteases (e.g., elastase inhibitors) or inhibition of Dipeptidyl peptidase 1 (DPP1/Cathepsin C) to prevent the N-terminal activation of NSPs during neutrophil maturation in the bone marrow.