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

Journal article
Authors Lisa Davidsson
Agnes Dahlstrand Rudin
Felix Peter Sanchez Klose
Alicia Buck
Lena Björkman
Karin Christenson
Johan Bylund
Published in International journal of molecular sciences
Volume 21
Issue 11
Pages E3750
ISSN 1422-0067
Publication year 2020
Published at Institute of Odontology
Institute of Medicine
Pages E3750
Language en
Links dx.doi.org/10.3390/ijms21113750
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Immunology

Abstract

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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