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Proteinase 3, Wegener’s autoantigen: from gene to antigen
Author(s) -
Geld Y. M.,
Limburg P. C.,
Kallenberg C. G. M.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.2.177
Subject(s) - proteinase 3 , cathepsin g , biology , proteases , azurophilic granule , myeloid leukemia , neutrophil elastase , serine protease , antigen , elastase , serine proteinase inhibitors , cathepsin c , immunology , leukemia , serine , microbiology and biotechnology , cytotoxic t cell , protease , inflammation , myeloperoxidase , enzyme , biochemistry , phosphorylation , in vitro
Proteinase 3 (PR3) is one of four serine protease homologues in the azurophilic granules of neutrophils and granules of monocytes. It is of importance that anti‐neutrophil cytoplasmic antibodies (ANCA) in patients with Wegener’s granulomatosis (WG) are mainly directed against PR3 only. Furthermore, PR3 is overexpressed in a variety of acute and chronic myeloid leukemia cells. Cytotoxic T lymphocytes specific for a PR3‐derived peptide have been shown to specifically lyse leukemia cells that overexpress PR3. This review will focus on PR3 and the characteristics of PR3 that might implicate this particular antigen in the pathogenesis of WG and as target for immunotherapy in myeloid leukemias. We will discuss the genetic localization and gene regulation of PR3, the processing, storage, and expression of the PR3 protein, and the physiological functions of PR3, and compare this with the three other neutrophil‐derived serine proteases: human leukocyte elastase, cathepsin G, and azurocidin. Three main differences are described between PR3 and the other serine proteases. This makes PR3 a very intriguing protein with a large array of physiological functions, some of which may play a role in ANCA‐associated vasculitidis and myeloid leukemia.