Neutrophil serine protease (Proteinase 3 and Cathepsin G) (PR3 and CatG)

Proteinase 3 (PR3) and Cathepsin G (CatG) are essential serine proteases stored within the azurophilic granules of neutrophils, playing a critical role in the innate immune response. These enzymes are responsible for the degradation of internalized pathogens and the processing of various pro-inflammatory cytokines, such as IL-1 beta and TNF-alpha, which orchestrate the inflammatory cascade [1, 2]. Under normal physiological conditions, their activity is tightly regulated by endogenous inhibitors like alpha-1 antitrypsin; however, excessive or persistent release into the extracellular space can lead to significant tissue destruction and chronic inflammatory diseases [4, 5]. PR3 is notably recognized as the primary autoantigen in granulomatosis with polyangiitis (GPA), where anti-neutrophil cytoplasmic antibodies (ANCA) trigger neutrophil activation and vascular damage [4]. In respiratory conditions like bronchiectasis and COPD, these proteases contribute to airway remodeling and mucus hypersecretion [5]. Therapeutic interventions focus on either direct inhibition of their catalytic activity or the inhibition of Dipeptidyl Peptidase 1 (DPP1), the enzyme required for their N-terminal activation during neutrophil maturation [3]. Targeting these proteases aims to reduce the inflammatory burden in chronic diseases while maintaining sufficient immune competence.

Other names

Proteinase 3Cathepsin GPRTN3CTSGMyeloblastinWegener autoantigenAzurophil granule protein 7AGEP

Inhibition of proteolytic activity through direct binding to the enzyme active site or prevention of enzyme maturation via inhibition of Dipeptidyl peptidase 1 (DPP1) [3, 5].