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Korkmaz, B.* ; Lesner, A.* ; Letast, S.* ; Mahdi, Y.K.* ; Jourdan, M.L.* ; Dallet-Choisy, S.* ; Marchand-Adam, S.* ; Kellenberger, C.* ; Viaud-Massuard, M.C.* ; Jenne, D. ; Gauthier, F.*

Neutrophil proteinase 3 and dipeptidyl peptidase I (cathepsin C) as pharmacological targets in granulomatosis with polyangiitis (Wegener granulomatosis).

Semin. Immunopathol. 35, 411-421 (2013)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Neutrophils are among the first cells implicated in acute inflammation. Leaving the blood circulation, they quickly migrate through the interstitial space of tissues and liberate oxidants and other antimicrobial proteins together with serine proteinases. Neutrophil elastase, cathepsin G, proteinase 3 (PR3), and neutrophil serine protease 4 are four hematopoietic serine proteases activated by dipeptidyl peptidase I during neutrophil maturation and are mainly stored in cytoplasmic azurophilic granules. They regulate inflammatory and immune responses after their release from activated neutrophils at inflammatory sites. Membrane-bound PR3 (mbPR3) at the neutrophil surface is the prime antigenic target of antineutrophil cytoplasmic autoantibodies (ANCA) in granulomatosis with polyangiitis (GPA), a vasculitis of small blood vessels and granulomatous inflammation of the upper and/or lower respiratory tracts. The interaction of ANCA with mbPR3 results in excessive activation of neutrophils to produce reactive oxygen species and liberation of granular proteinases to the pericellular environment. In this review, we focus on PR3 and dipeptidyl peptidase I as attractive pharmacological targets whose inhibition is expected to attenuate autoimmune activation of neutrophils in GPA.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter Proteinase3; Dipeptidyl peptidase I (cathepsin C); Neutrophil; Granulomatosis with polyangiitis; ANCA; Antineutrophil Cytoplasmic Antibodies ; Human Polymorphonuclear Neutrophils ; Positive Systemic Vasculitis ; Antiproteinase 3 Antibodies ; Papillon-lefevre-syndrome ; Fc-gamma-riiib ; Serine Proteases ; Membrane Proteinase-3 ; Antigen Proteinase-3 ; Catalytic-activity
ISSN (print) / ISBN 1863-2297
Zeitschrift Seminars in Immunopathology
Quellenangaben Band: 35, Heft: 4, Seiten: 411-421 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort Berlin ; Heidelberg
Begutachtungsstatus