7 results match your criteria: "Munich and Max-Planck Institute of Neurobiology[Affiliation]"
Constitutive and induced forms of membrane-bound proteinase 3 interact with antineutrophil cytoplasmic antibodies and promote immune activation of neutrophils.
J Biol Chem
April 2023
INSERM UMR-1100, "Research Center for Respiratory Diseases" and University of Tours, Tours, France. Electronic address:
Proteinase 3 (PR3) is the main target antigen of antineutrophil cytoplasmic antibodies (ANCAs) in PR3-ANCA-associated vasculitis. A small fraction of PR3 is constitutively exposed on the surface of quiescent blood neutrophils in a proteolytically inactive form. When activated, neutrophils expose an induced form of membrane-bound PR3 (PR3) on their surface as well, which is enzymatically less active than unbound PR3 in solution due to its altered conformation.
View Article and Find Full Text PDFPathogenicity of Proteinase 3-Anti-Neutrophil Cytoplasmic Antibody in Granulomatosis With Polyangiitis: Implications as Biomarker and Future Therapies.
Front Immunol
June 2021
Université de Tours, Plateforme B Cell Ressources (BCR) EA4245, Tours, France.
Article Synopsis
- - Granulomatosis with polyangiitis (GPA) is a serious autoimmune disease that causes blood vessel inflammation and is often linked to a specific antibody known as Anti-Neutrophil Cytoplasmic Antibody (ANCA), particularly the PR3-ANCA type.
- - Despite existing treatments, GPA remains a challenging condition with high mortality and relapse rates, and current methods to track disease activity using PR3-ANCA levels can be unreliable in about 25% of cases.
- - The review highlights the need for new biomarkers and therapies by examining factors that influence the pathogenicity of PR3-ANCA, such as its interaction with neutrophils and specific characteristics like glycosylation, aiming for
Proteinase release from activated neutrophils in mechanically ventilated patients with non-COVID-19 and COVID-19 pneumonia.
Eur Respir J
April 2021
INSERM UMR-1100, "Research Center for Respiratory Diseases", University of Tours, Tours, France.
https://bit.ly/3nihveh
View Article and Find Full Text PDFLung Protection by Cathepsin C Inhibition: A New Hope for COVID-19 and ARDS?
J Med Chem
November 2020
Comprehensive Pneumology Center, Institute of Lung Biology and Disease, German Center for Lung Research (DZL), Munich and Max-Planck Institute of Neurobiology, 82152 Planegg-Martinsried, Germany.
Cathepsin C (CatC) is a cysteine dipeptidyl aminopeptidase that activates most of tissue-degrading elastase-related serine proteases. Thus, CatC appears as a potential therapeutic target to impair protease-driven tissue degradation in chronic inflammatory and autoimmune diseases. A depletion of proinflammatory elastase-related proteases in neutrophils is observed in patients with CatC deficiency (Papillon-Lefèvre syndrome).
View Article and Find Full Text PDFExploiting the S4-S5 Specificity of Human Neutrophil Proteinase 3 to Improve the Potency of Peptidyl Di(chlorophenyl)-phosphonate Ester Inhibitors: A Kinetic and Molecular Modeling Analysis.
J Med Chem
March 2018
INSERM UMR1100, "Centre d'Etude des Pathologies Respiratoires" , Université de Tours, 37032 Tours , France.
The neutrophilic serine protease proteinase 3 (PR3) is involved in inflammation and immune response and thus appears as a therapeutic target for a variety of infectious and inflammatory diseases. Here we combined kinetic and molecular docking studies to increase the potency of peptidyl-diphenyl phosphonate PR3 inhibitors. Occupancy of the S1 subsite of PR3 by a nVal residue and of the S4-S5 subsites by a biotinylated Val residue as obtained in biotin-VYDnV(O-CH-4-Cl) enhanced the second-order inhibition constant k/[I] toward PR3 by more than 10 times ( k/[I] = 73000 ± 5000 M s) as compared to the best phosphonate PR3 inhibitor previously reported.
View Article and Find Full Text PDFNeutrophilic Cathepsin C Is Maturated by a Multistep Proteolytic Process and Secreted by Activated Cells during Inflammatory Lung Diseases.
J Biol Chem
April 2016
From the INSERM U-1100, "Centre d'Etude des Pathologies Respiratoires" and Université François Rabelais, 37032, Tours, France,
Article Synopsis
- - The enzyme cathepsin C (CatC) plays a role in activating inflammatory proteases in precursor immune cells, and inhibiting it early in bone marrow could help treat chronic inflammatory diseases.
- - Research into CatC's maturation reveals it follows a multistep process managed by another enzyme, cathepsin S (CatS), and blocking CatS significantly reduces CatC activity while not entirely halting other neutrophil proteases.
- - In patients with lung inflammation, activated neutrophils secrete large amounts of mature CatC, and ongoing clinical trials for CatS inhibitors aim to target CatC activity specifically, potentially reducing inflammation without affecting other important proteases.
New selective peptidyl di(chlorophenyl) phosphonate esters for visualizing and blocking neutrophil proteinase 3 in human diseases.
J Biol Chem
November 2014
INSERM U-1100/EA-6305 Centre d'Etude des Pathologies Respiratoires and Université François Rabelais, 37032 Tours, France,. Electronic address:
The function of neutrophil protease 3 (PR3) is poorly understood despite of its role in autoimmune vasculitides and its possible involvement in cell apoptosis. This makes it different from its structural homologue neutrophil elastase (HNE). Endogenous inhibitors of human neutrophil serine proteases preferentially inhibit HNE and to a lesser extent, PR3.
View Article and Find Full Text PDF