Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1783549824988086272 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7312864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT davidssonlisa invivotransmigratedhumanneutrophilsarehighlyprimedforintracellularradicalproductioninducedbymonosodiumuratecrystals AT dahlstrandrudinagnes invivotransmigratedhumanneutrophilsarehighlyprimedforintracellularradicalproductioninducedbymonosodiumuratecrystals AT sanchezklosefelixpeter invivotransmigratedhumanneutrophilsarehighlyprimedforintracellularradicalproductioninducedbymonosodiumuratecrystals AT buckalicia invivotransmigratedhumanneutrophilsarehighlyprimedforintracellularradicalproductioninducedbymonosodiumuratecrystals AT bjorkmanlena invivotransmigratedhumanneutrophilsarehighlyprimedforintracellularradicalproductioninducedbymonosodiumuratecrystals AT christensonkarin invivotransmigratedhumanneutrophilsarehighlyprimedforintracellularradicalproductioninducedbymonosodiumuratecrystals AT bylundjohan invivotransmigratedhumanneutrophilsarehighlyprimedforintracellularradicalproductioninducedbymonosodiumuratecrystals |