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Bonding the foe – NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals

In the presence of sodium, uric acid from purine metabolism precipitates as monosodium urate (MSU) needles and forms renal calculi or causes gouty arthritis in kidneys and joints, respectively. The latter is characterized by red, hot, and swollen arthritic joints. Here we report the in vitro effect...

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Autores principales: Schorn, Christine, Janko, Christina, Krenn, Veit, Zhao, Yi, Munoz, Luis E., Schett, Georg, Herrmann, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517988/
https://www.ncbi.nlm.nih.gov/pubmed/23233855
http://dx.doi.org/10.3389/fimmu.2012.00376
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author Schorn, Christine
Janko, Christina
Krenn, Veit
Zhao, Yi
Munoz, Luis E.
Schett, Georg
Herrmann, Martin
author_facet Schorn, Christine
Janko, Christina
Krenn, Veit
Zhao, Yi
Munoz, Luis E.
Schett, Georg
Herrmann, Martin
author_sort Schorn, Christine
collection PubMed
description In the presence of sodium, uric acid from purine metabolism precipitates as monosodium urate (MSU) needles and forms renal calculi or causes gouty arthritis in kidneys and joints, respectively. The latter is characterized by red, hot, and swollen arthritic joints. Here we report the in vitro effect of MSU crystals on blood granulocytes and analyze their contribution to granuloma formation and neutrophil extracellular traps (NETs) formation (NETosis) in synovial fluid of patients with gouty arthritis in vivo. We observed that MSU crystals induce NETosis in vitro in a reactive oxygen species (ROS)-dependent manner. Indeed, blocking ROS (e.g., the oxidative burst) by various anti-oxidants partially inhibited NETosis induced by MSU crystals. Analyses of synovial fluids and of tissue sections of patients suffering from gout revealed that NETs are also formed in vivo, especially during acute gouty flares and/or granuloma formation. Since prolonged exposure to NETs carries the risk for the development of chronic inflammation we also studied the opsonization of NETs, as a prerequisite for their clearance. The established dead cells’ opsonins C3b, galectin-9, and CRP decorated the residual dead cells’ corpses and opsonized these for disposal. Surprisingly, all three soluble pattern recognizing molecules spared the spread NET structures. We conclude that (i) MSU crystals are strong inducers of ROS-dependent NETosis and (ii) that the prolonged presence of NET-pathogen or NET-crystal aggregates observed in patients with systemic autoimmunity, especially in those with low serum DNase-1 activity, cannot be compensated by CRP, complement, and galectin-mediated phagocytic clearance.
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spelling pubmed-35179882012-12-11 Bonding the foe – NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals Schorn, Christine Janko, Christina Krenn, Veit Zhao, Yi Munoz, Luis E. Schett, Georg Herrmann, Martin Front Immunol Immunology In the presence of sodium, uric acid from purine metabolism precipitates as monosodium urate (MSU) needles and forms renal calculi or causes gouty arthritis in kidneys and joints, respectively. The latter is characterized by red, hot, and swollen arthritic joints. Here we report the in vitro effect of MSU crystals on blood granulocytes and analyze their contribution to granuloma formation and neutrophil extracellular traps (NETs) formation (NETosis) in synovial fluid of patients with gouty arthritis in vivo. We observed that MSU crystals induce NETosis in vitro in a reactive oxygen species (ROS)-dependent manner. Indeed, blocking ROS (e.g., the oxidative burst) by various anti-oxidants partially inhibited NETosis induced by MSU crystals. Analyses of synovial fluids and of tissue sections of patients suffering from gout revealed that NETs are also formed in vivo, especially during acute gouty flares and/or granuloma formation. Since prolonged exposure to NETs carries the risk for the development of chronic inflammation we also studied the opsonization of NETs, as a prerequisite for their clearance. The established dead cells’ opsonins C3b, galectin-9, and CRP decorated the residual dead cells’ corpses and opsonized these for disposal. Surprisingly, all three soluble pattern recognizing molecules spared the spread NET structures. We conclude that (i) MSU crystals are strong inducers of ROS-dependent NETosis and (ii) that the prolonged presence of NET-pathogen or NET-crystal aggregates observed in patients with systemic autoimmunity, especially in those with low serum DNase-1 activity, cannot be compensated by CRP, complement, and galectin-mediated phagocytic clearance. Frontiers Media S.A. 2012-12-10 /pmc/articles/PMC3517988/ /pubmed/23233855 http://dx.doi.org/10.3389/fimmu.2012.00376 Text en Copyright © Schorn, Janko, Krenn, Zhao, Munoz, Schett and Herrmann. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Immunology
Schorn, Christine
Janko, Christina
Krenn, Veit
Zhao, Yi
Munoz, Luis E.
Schett, Georg
Herrmann, Martin
Bonding the foe – NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals
title Bonding the foe – NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals
title_full Bonding the foe – NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals
title_fullStr Bonding the foe – NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals
title_full_unstemmed Bonding the foe – NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals
title_short Bonding the foe – NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals
title_sort bonding the foe – netting neutrophils immobilize the pro-inflammatory monosodium urate crystals
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517988/
https://www.ncbi.nlm.nih.gov/pubmed/23233855
http://dx.doi.org/10.3389/fimmu.2012.00376
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