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In Vivo Transmigrated Human Neutrophils Are Highly Primed for Intracellular Radical Production Induced by Monosodium Urate Crystals

Gout is an inflammatory disease caused by monosodium urate (MSU) crystals. The role of neutrophils in gout is less clear, although several studies have shown neutrophil extracellular trap (NET) formation in acutely inflamed joints of gout patients. MSU crystals are known to induce the production of...

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Autores principales: Davidsson, Lisa, Dahlstrand Rudin, Agnes, Sanchez Klose, Felix Peter, Buck, Alicia, Björkman, Lena, Christenson, Karin, Bylund, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312864/
https://www.ncbi.nlm.nih.gov/pubmed/32466527
http://dx.doi.org/10.3390/ijms21113750
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author Davidsson, Lisa
Dahlstrand Rudin, Agnes
Sanchez Klose, Felix Peter
Buck, Alicia
Björkman, Lena
Christenson, Karin
Bylund, Johan
author_facet Davidsson, Lisa
Dahlstrand Rudin, Agnes
Sanchez Klose, Felix Peter
Buck, Alicia
Björkman, Lena
Christenson, Karin
Bylund, Johan
author_sort Davidsson, Lisa
collection PubMed
description Gout is an inflammatory disease caused by monosodium urate (MSU) crystals. The role of neutrophils in gout is less clear, although several studies have shown neutrophil extracellular trap (NET) formation in acutely inflamed joints of gout patients. MSU crystals are known to induce the production of reactive oxygen species (ROS) and NET formation in neutrophils isolated from blood, but there is inconclusive knowledge on the localization of ROS production as well as whether the ROS are required for NET formation. In this report we demonstrate that MSU crystals activate human neutrophils to produce ROS exclusively in intracellular compartments. Additionally, in vivo transmigrated neutrophils derived from experimental skin chambers displayed markedly increased ROS production as compared to resting blood neutrophils. We also confirmed that MSU stimulation potently induced NET formation, but this response was not primed in in vivo transmigrated neutrophils. In line with this we found that MSU-triggered NET formation was independent of ROS production and proceeded normally in neutrophils from patients with dysfunctional respiratory burst (chronic granulomatous disease (CGD) and complete myeloperoxidase (MPO) deficiency). Our data indicate that in vivo transmigrated neutrophils are markedly primed for oxidative responses to MSU crystals and that MSU triggered NET formation is independent of ROS production.
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spelling pubmed-73128642020-06-29 In Vivo Transmigrated Human Neutrophils Are Highly Primed for Intracellular Radical Production Induced by Monosodium Urate Crystals Davidsson, Lisa Dahlstrand Rudin, Agnes Sanchez Klose, Felix Peter Buck, Alicia Björkman, Lena Christenson, Karin Bylund, Johan Int J Mol Sci Article Gout is an inflammatory disease caused by monosodium urate (MSU) crystals. The role of neutrophils in gout is less clear, although several studies have shown neutrophil extracellular trap (NET) formation in acutely inflamed joints of gout patients. MSU crystals are known to induce the production of reactive oxygen species (ROS) and NET formation in neutrophils isolated from blood, but there is inconclusive knowledge on the localization of ROS production as well as whether the ROS are required for NET formation. In this report we demonstrate that MSU crystals activate human neutrophils to produce ROS exclusively in intracellular compartments. Additionally, in vivo transmigrated neutrophils derived from experimental skin chambers displayed markedly increased ROS production as compared to resting blood neutrophils. We also confirmed that MSU stimulation potently induced NET formation, but this response was not primed in in vivo transmigrated neutrophils. In line with this we found that MSU-triggered NET formation was independent of ROS production and proceeded normally in neutrophils from patients with dysfunctional respiratory burst (chronic granulomatous disease (CGD) and complete myeloperoxidase (MPO) deficiency). Our data indicate that in vivo transmigrated neutrophils are markedly primed for oxidative responses to MSU crystals and that MSU triggered NET formation is independent of ROS production. MDPI 2020-05-26 /pmc/articles/PMC7312864/ /pubmed/32466527 http://dx.doi.org/10.3390/ijms21113750 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Davidsson, Lisa
Dahlstrand Rudin, Agnes
Sanchez Klose, Felix Peter
Buck, Alicia
Björkman, Lena
Christenson, Karin
Bylund, Johan
In Vivo Transmigrated Human Neutrophils Are Highly Primed for Intracellular Radical Production Induced by Monosodium Urate Crystals
title In Vivo Transmigrated Human Neutrophils Are Highly Primed for Intracellular Radical Production Induced by Monosodium Urate Crystals
title_full In Vivo Transmigrated Human Neutrophils Are Highly Primed for Intracellular Radical Production Induced by Monosodium Urate Crystals
title_fullStr In Vivo Transmigrated Human Neutrophils Are Highly Primed for Intracellular Radical Production Induced by Monosodium Urate Crystals
title_full_unstemmed In Vivo Transmigrated Human Neutrophils Are Highly Primed for Intracellular Radical Production Induced by Monosodium Urate Crystals
title_short In Vivo Transmigrated Human Neutrophils Are Highly Primed for Intracellular Radical Production Induced by Monosodium Urate Crystals
title_sort in vivo transmigrated human neutrophils are highly primed for intracellular radical production induced by monosodium urate crystals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312864/
https://www.ncbi.nlm.nih.gov/pubmed/32466527
http://dx.doi.org/10.3390/ijms21113750
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