Review: Neutrophils as Invigorated Targets in Rheumatic Diseases

Grayson, Peter C.; Schauer, Christine; Herrmann, Martin; Kaplan, Mariana J.

doi:10.1002/art.39745

Cited by 24 publications

(25 citation statements)

References 91 publications

(119 reference statements)

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“…Standards of levamisole (Sigma-Aldrich), 13 C 6 -D-levamisole (AlsaChim), D 3 -cocaine (Sigma-Aldrich), and 250 μg/ml certified reference material Cocaine Multi-Component Cocaine Mixture (Sigma-Aldrich, C-088-1ML) were obtained. The drugs and metabolites were extracted from urine by vortexing a 25-μl aliquot of urine and 475 μl water with 0.1% formic acid containing 13 C 6 -D-levamisole and D 3 -cocaine internal standards for 5 minutes.…”

Section: Endothelial Cytotoxicity Assaymentioning

confidence: 99%

“…Most of the prior investigations into the mechanisms of drug-induced autoimmunity have focused upon the effects of these medications on mononuclear cells. The potential contributions of neutrophils to drug-induced autoimmunity have not been extensively studied, yet neutrophil dysregulation plays an increasingly recognized role in the pathogenesis of certain autoimmune diseases including AAV and SLE (13).…”

Section: Introductionmentioning

confidence: 99%

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A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity

et al. 2017

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Section: Endothelial Cytotoxicity Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity

et al. 2017

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“…There is growing evidence indicating that neutrophils have an active role in the pathogenesis of RA . Inflammatory joint effusions of RA patients are characterized by a high number of neutrophils in the SF where these cells mediate tissue destruction after improper activation . The aim of the present study was to analyze the characteristics of neutrophils infiltrating the inflamed joints in the presence of ACPA autoantibodies in SF of RA patients.…”

Section: Discussionmentioning

confidence: 97%

“…In fact, the generation of proteins modified by citrullination in the joint by activation of PADs is a key stage to trigger anticitrulline immunity in ACPA-positive patients [31]. Thus, NET formation is likely to play a pathogenic role in RA as NETosis may serve as an important source of citrullinated autoantigens [4]. Although this study involved a relatively low number of SF samples, we observed that in vitro incubation of neutrophils with ACPA high SF resulted in an increase of ROS production in PMA-primed cells, and also in extracellular DNA release.…”

Section: Discussionmentioning

confidence: 99%

Association between levels of synovial anti‐citrullinated peptide antibodies and neutrophil response in patients with rheumatoid arthritis

Gorlino

Dave

Blas³

et al. 2018

Eur J Immunol

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Rheumatoid arthritis (RA) is characterized by the presence of anti-citrullinated peptide antibodies (ACPAs) and neutrophils infiltrating the synovial fluid (SF) of the affected joints. The aim of this work was to analyze whether the presence of ACPAs in SF is associated with neutrophil infiltration and with their phenotype in the inflamed joints of RA patients. We found that in the presence of ACPAs, the number of synovial neutrophils correlated with severe disease activity. The SF were divided according to synovial ACPA levels in negative- (<25 U/mL), low- (25-200 U/mL) and high level (˃200 U/mL; ACPA ). We observed that IL-6, IL-17, and IL-8 were significantly elevated in ACPA SF and that IL-8 levels correlated positively with neutrophil counts and with worse clinical manifestations. Additionally, in vitro incubation of neutrophils with ACPA SF resulted in an increased ROS production and extracellular DNA release compared to neutrophils incubated with ACPA-negative SF. These exacerbated effector functions were associated with a fraction of ICAM-1-positive neutrophils, which were induced by ACPA SF. Likewise, in in vivo, we could also detect this subset among neutrophils present in ACPA SF. In conclusion, the data presented here shed light on the role of SF-ACPAs as inductors of a proinflammatory profile in neutrophils.

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“…These structures in turn are bound by autoantibodies, commonly found in the blood of SLE patients, and this leads to their uptake by plasmacytoid dendritic cells and stimulation of interferon production. This vicious cycle of interferon-driven neutrophil activation is proposed to be a potential target of therapeutic intervention in SLE [23]. …”

Section: Neutrophil Heterogeneity – Not All Neutrophils Are Equalmentioning

confidence: 99%

Expanding Neutrophil Horizons: New Concepts in Inflammation

2018

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Research into neutrophil biology in the last 10 years has uncovered a number of unexpected aspects of this still mysterious innate immune cell. Advances in technology have allowed visualisation of neutrophil trafficking to sites of inflammation, and, remarkably, neutrophils have been observed to depart from the scene in what has been termed reverse migration. There has also been increasing appreciation of the heterogeneity of neutrophils with ongoing categorisation of neutrophil subsets, including myeloid-derived suppressor cells and low-density granulocytes. Newly recognised neutrophil functions include the ability to release novel immune mediators such as extracellular DNA and microvesicles. Finally, studies of neutrophil cell death, both apoptotic and non-apoptotic, have revealed remarkable differences compared to other cell types. This review will highlight important discoveries in these facets of neutrophil biology and how the new findings will inform treatment of diseases where neutrophils are implicated.

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Review: Neutrophils as Invigorated Targets in Rheumatic Diseases

Abstract: OLFM4 5 olfactomedin 4; ANCA 5 antineutrophil cytoplasmic antibody; ROS 5 reactive oxygen species; SLE 5 systemic lupus erythematosus; NETs 5 neutrophil extracellular traps.

Cited by 24 publications

References 91 publications

A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity

A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity

Association between levels of synovial anti‐citrullinated peptide antibodies and neutrophil response in patients with rheumatoid arthritis

Expanding Neutrophil Horizons: New Concepts in Inflammation

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