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Citations to this article

Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin
Kai Kessenbrock, … , Reinhard Fässler, Dieter E. Jenne
Kai Kessenbrock, … , Reinhard Fässler, Dieter E. Jenne
Published June 20, 2008
Citation Information: J Clin Invest. 2008;118(7):2438-2447. https://doi.org/10.1172/JCI34694.
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Research Article Inflammation Article has an altmetric score of 8

Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin

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Abstract

Neutrophil granulocytes form the body’s first line of antibacterial defense, but they also contribute to tissue injury and noninfectious, chronic inflammation. Proteinase 3 (PR3) and neutrophil elastase (NE) are 2 abundant neutrophil serine proteases implicated in antimicrobial defense with overlapping and potentially redundant substrate specificity. Here, we unraveled a cooperative role for PR3 and NE in neutrophil activation and noninfectious inflammation in vivo, which we believe to be novel. Mice lacking both PR3 and NE demonstrated strongly diminished immune complex–mediated (IC-mediated) neutrophil infiltration in vivo as well as reduced activation of isolated neutrophils by ICs in vitro. In contrast, in mice lacking just NE, neutrophil recruitment to ICs was only marginally impaired. The defects in mice lacking both PR3 and NE were directly linked to the accumulation of antiinflammatory progranulin (PGRN). Both PR3 and NE cleaved PGRN in vitro and during neutrophil activation and inflammation in vivo. Local administration of recombinant PGRN potently inhibited neutrophilic inflammation in vivo, demonstrating that PGRN represents a crucial inflammation-suppressing mediator. We conclude that PR3 and NE enhance neutrophil-dependent inflammation by eliminating the local antiinflammatory activity of PGRN. Our results support the use of serine protease inhibitors as antiinflammatory agents.

Authors

Kai Kessenbrock, Leopold Fröhlich, Michael Sixt, Tim Lämmermann, Heiko Pfister, Andrew Bateman, Azzaq Belaaouaj, Johannes Ring, Markus Ollert, Reinhard Fässler, Dieter E. Jenne

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 Total
Citations: 4 10 11 11 19 17 14 9 10 15 14 16 18 15 16 7 8 214
Citation information
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Citations to this article in year 2011 (16)

Title and authors Publication Year
Cleavage of the CD11b extracellular domain by the leukocyte serprocidins is critical for neutrophil detachment during chemotaxis
K Zen, YL Guo, LM Li, Z Bian, CY Zhang, Y Liu
Blood 2011
Netting neutrophils induce endothelial damage, infiltrate tissues and expose immunostimulatory molecules in systemic lupus erythematosus*
E Villanueva, S Yalavarthi, CC Berthier, JB Hodgin, R Khandpur, AM Lin, CJ Rubin, W Zhao, SH Olsen, M Klinker, D Shealy, MF Denny, J Plumas, L Chaperot, M Kretzler, AT Bruce, MJ Kaplan
Journal of immunology (Baltimore, Md. : 1950) 2011
Rescue of Progranulin Deficiency Associated with Frontotemporal Lobar Degeneration by Alkalizing Reagents and Inhibition of Vacuolar ATPase
A Capell, S Liebscher, K Fellerer, N Brouwers, M Willem, S Lammich, I Gijselinck, T Bittner, AM Carlson, F Sasse, B Kunze, H Steinmetz, R Jansen, D Dormann, K Sleegers, M Cruts, J Herms, CV Broeckhoven, C Haass
The Journal of neuroscience : the official journal of the Society for Neuroscience 2011
SerpinB1 protects the mature neutrophil reserve in the bone marrow
C Benarafa, TE LeCuyer, M Baumann, JM Stolley, TP Cremona, E Remold-O'Donnell
Journal of leukocyte biology 2011
T-helper cells as new players in ANCA-associated vasculitides
WH Abdulahad, P Lamprecht, CG Kallenberg
Arthritis Research & Therapy 2011
Progranulin: A promising therapeutic target for rheumatoid arthritis
C Liu
FEBS Letters 2011
Cellular Effects of Progranulin in Health and Disease
LD Muynck, PV Damme
Journal of Molecular Neuroscience 2011
Structure, Function, and Mechanism of Progranulin; the Brain and Beyond
H Toh, BP Chitramuthu, HP Bennett, A Bateman
Journal of Molecular Neuroscience 2011
Loss of function mutations in the progranulin gene are related to pro-inflammatory cytokine dysregulation in frontotemporal lobar degeneration patients
P Bossù, F Salani, A Alberici, S Archetti, G Bellelli, D Galimberti, E Scarpini, G Spalletta, C Caltagirone, A Padovani, B Borroni
Journal of Neuroinflammation 2011
Mucosal Progranulin expression is induced by H. pylori, but independent of Secretory Leukocyte Protease Inhibitor (SLPI) expression
T Wex, D Kuester, C Schönberg, D Schindele, G Treiber, P Malfertheiner
BMC Gastroenterology 2011
The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice
W Tang, Y Lu, QY Tian, Y Zhang, FJ Guo, GY Liu, NM Syed, Y Lai, EA Lin, L Kong, J Su, F Yin, AH Ding, A Zanin-Zhorov, ML Dustin, J Tao, J Craft, Z Yin, JQ Feng, SB Abramson, XP Yu, C Liu
Science (New York, N.Y.) 2011
Low plasma progranulin levels in children with autism
LY Al-Ayadhi, GA Mostafa
Journal of Neuroinflammation 2011
Thymic stromal lymphopoetin-induced expression of the endogenous inhibitory enzyme SLPI mediates recovery from colonic inflammation
C Reardon, M Lechmann, A Brüstle, MG Gareau, N Shuman, D Philpott, SF Ziegler, TW Mak
Immunity 2011
Progranulin Is a Chemoattractant for Microglia and Stimulates Their Endocytic Activity
F Pickford, J Marcus, LM Camargo, Q Xiao, D Graham, JR Mo, M Burkhardt, V Kulkarni, J Crispino, H Hering, M Hutton
The American Journal of Pathology 2011
Extracellular progranulin protects cortical neurons from toxic insults by activating survival signaling
J Xu, M Xilouri, J Bruban, J Shioi, Z Shao, I Papazoglou, K Vekrellis, NK Robakis
Neurobiology of Aging 2011
Potential mechanisms of progranulin-deficient FTLD
ME Ward, BL Miller
Journal of molecular neuroscience : MN 2011

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