title: Human proteinase 3 (PR3) and its binding molecules: implications for inflammatory and PR3-related autoimmune responses.
abstract: Human proteinase 3 (PR3) is a multifunctional serine protease, mainly located in the azurophilic granules and on the cell surface of polymorphonuclear leukocytes (PMN). Cumulated data indicate that PR3, which is the main target autoantigen of antineutrophilic cytoplasmic antibodies (ANCA), interacts with several surface receptors and participates in the local inflammatory response. Herein, we summarize the efforts made to elucidate ANCA-binding epitopes of PR3, extended by data derived from the use of a random peptide library. The inserts for 107 peptides were obtained by panning of a random peptide library with PR3-ANCA(+) immunoglobulins. Analysis of the amino acid sequences of the inserted peptides derived from isolated positive clones suggested that they do not belong to linear epitopes of PR03 and possess a high proportion of positively charged amino acids. Furthermore, this article focuses on immune functions of PR3 with respect to PR3 modulation of cell activation via cleavage of protease-activated receptor-2 (PAR-2) and as binding protein for the proinflammatory cytokine IL-32alpha. Altogether, there are a number of (auto)molecules that bind to PR3, some of them even competitive and each binding interaction seems to have specific implications.
authors.affiliation: Department of Rheumatology, University of Luebeck, Germany. mueller@mail.uni-luebeck.de
authors.forename: Antje
authors.initials: A
authors.lastname: Müller
authors.forename: Jan
authors.initials: J
authors.lastname: Voswinkel
authors.forename: Stefan
authors.initials: S
authors.lastname: Gottschlich
authors.forename: Elena
authors.initials: E
authors.lastname: Csernok
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007378:Interleukins / Q000378:metabolism; D053146:Myeloblastin / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding; D044464:Receptor, PAR-2 / Q000378:metabolism