Myeloblastin (Neutrophil proteinase 3) (PR3)

Myeloblastin, also widely known as Proteinase 3 (PR3), is a chymotrypsin-like serine protease primarily sequestered within the azurophilic granules of neutrophils [1, 2]. It plays a pivotal role in the innate immune response by degrading various extracellular matrix proteins, such as elastin, collagen, and fibronectin, and by activating pro-inflammatory cytokines like TNF-alpha and IL-1beta [2, 6]. Myeloblastin is the primary autoantigen targeted by antineutrophil cytoplasmic antibodies (c-ANCA) in Granulomatosis with Polyangiitis (GPA), where the binding of these antibodies triggers neutrophil activation and systemic vasculitis [6, 12]. In addition to its role in inflammation, the protein is overexpressed in myeloid leukemias and appears to influence the proliferation and differentiation of hematopoietic cells [3, 4]. Therapeutic efforts focus on developing selective serine protease inhibitors to mitigate tissue damage and utilizing immunomodulatory therapies to suppress the autoantibody response associated with vasculitis [11, 13].

Other names

Proteinase 3Leukocyte proteinase 3PR-3Wegener autoantigenC-ANCA antigenAzurophil granule protein 7AGP7Neutrophil proteinase 4P29MBN

Serine protease inhibition