Neutrophils in rheumatoid arthritis: More than simple final effectors (2022)

Table of Contents
Autoimmunity Reviews Abstract Introduction Section snippets Immune mediators production Conclusion Take-home messages Acknowledgments References (40) Am J Pathol Int J Biochem Cell Biol FEBS Lett J Autoimmun J Autoimmun Cell Immunol J Autoimmun Autoimmun Rev Blood Neutrophils and immunity: challenges and opportunities Nat Rev Immunol Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing Nat Med Secretion of oncostatin M by neutrophils in rheumatoid arthritis Arthritis Rheum Expression and regulation of CCL18 in synovial fluid neutrophils of patients with rheumatoid arthritis Arthritis Res Ther Expression of vascular endothelial growth factor by synovial fluid neutrophils in rheumatoid arthritis (RA) Clin Exp Immunol Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases Arthritis Rheum Tumor necrosis factor alpha activates release of B lymphocyte stimulator by neutrophils infiltrating the rheumatoid joint Arthritis Rheum Citrullination of synovial proteins in murine models of rheumatoid arthritis Arthritis Rheum Granulocyte colony-stimulating factor and neutrophils—forgotten mediators of inflammatory disease Nat Clin Pract Rheumatol Phagocyte-derived reactive oxygen species as suppressors of inflammatory disease Arthritis Rheum Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS-independent activation of NF-kappa B Eur J Immunol Cited by (159) Recommended articles (6) FAQs Videos
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Autoimmunity Reviews

Volume 9, Issue 8,

June 2010

, Pages 531-535

Abstract

Rheumatoid arthritis is the most common inflammatory joint disease. The etiopathogenesis of this condition has been classically explained by a T cell-driven process. However, recent studies have highlighted the possible contribution of neutrophils for the early phases of RA physiopathology. These cells are phagocytic leukocytes that play crucial roles in the acute defense against pathogens while modulating the function of other immune cells and contributing to the perpetuation of an initial inflammatory response. The herein article reviews recent progresses in the understanding of the immunopathology of RA with a special emphasis on the role of neutrophils.

Introduction

Rheumatoid arthritis (RA) is a chronic immune inflammatory disease characterized by synovial hyperplasia, joint destruction and extra-articular manifestations with a significant impact on both morbidity and mortality. Although the etiopathology of this condition is not fully understood, it is known that neutrophils, macrophages, synovial fibroblasts, T cells and B cells are involved in the mechanisms that drive the onset of RA. T cells, B cells and macrophages infiltrate the synovium and form discrete lymphoid aggregates, sometimes with ectopic germinal centers, while macrophage-like and fibroblast-like synoviocytes accumulate in the intima causing hyperplasia and secreting degradative enzymes. However, before these events take place, neutrophils migrate to the synovial fluid (SF) where they phagocyte immune complexes and release powerful proteases. Neutrophils, which are part of the innate immunity, are crucial for pathogenic defense. They are the first cell type to arrive at sites of inflammation, followed by monocytes [1]. In a normal inflammatory response and upon appropriate stimuli, neutrophils are able to release cytotoxic mediators, such as reactive oxygen (ROS) and nitrogen (RNS) species and proteases into the extracellular space, generating damage to the pathogen and to the host tissues. Consequently, and after elimination of the pro-inflammatory stimulus, there is an urgent need to repair the injuries and return to a state of homeostasis. This is manifested as a shift towards anti-inflammatory signals that ultimately lead to the resolution of inflammation. At this point, neutrophils must die by apoptosis and be ingested by macrophages that are involved in clearing the inflamed area. Concomitantly, anti-inflammatory signals such as macrophage-derived lipoxins stop the influx of neutrophils and activate macrophages to phagocyte dead cells, thus pushing the inflammatory response towards resolution of inflammation [2]. In RA the mechanisms of neutrophil activation, recruitment and apoptosis are altered. This review is focused on recent developments in the immunobiology of RA, specifically regarding the contribution of neutrophils for disease progression.

Section snippets

Immune mediators production

Mature neutrophils have been considered terminally differentiated cells that have a low level of de novo protein synthesis. However, neutrophils were shown to synthesize a large variety of cytokines and chemokines under inflammatory conditions. Although neutrophils produce lower amounts of these molecules than other cells, their higher number at inflammatory sites makes them an important source for these proteins. Cytokines and chemokines are crucial to amplify inflammation, by recruiting more

Conclusion

The traditional concept of the neutrophil as a professional phagocytic cell only able to destroy pathogens and tissues seems to be at odds with recently obtained data. Neutrophils in chronic inflammatory settings, as is the case of RA, are able to interact with other cells and to regulate their functions. They produce inflammatory mediators that contribute to the regulation of the inflammatory process and are able to adopt different phenotypes like APC or osteoclasts. In summary, neutrophils

Take-home messages

Neutrophils are the first cell type to arrive at sites of inflammation.

Under chronic inflammatory conditions neutrophils are able to release protease-rich granules and to produce high amounts of ROS.

Neutrophils secrete immune mediators which can activate themselves and other immune cells, triggering positive regulatory feedbacks which lead to acute and persistent inflammation.

Neutrophils live longer in inflammatory sites, augmenting the release of powerful destructive enzymes.

Neutrophils are

Acknowledgments

This work was supported by a fellowship from Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/40513/2007 and partially supported by a grant from Sociedade Portuguesa de Reumatologia and FCT grant PTDC/SAU-OSM/73449/2006.

(Video) Neutrophil Contribution to Inflammation and Autoimmunity in Rheumatic Disease

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    Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing

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    (Video) Neutrophils in Inflammation and Autoimmunity

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    Secretion of oncostatin M by neutrophils in rheumatoid arthritis

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    Expression and regulation of CCL18 in synovial fluid neutrophils of patients with rheumatoid arthritis

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    Citrullination of synovial proteins in murine models of rheumatoid arthritis

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    Granulocyte colony-stimulating factor and neutrophils—forgotten mediators of inflammatory disease

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    Phagocyte-derived reactive oxygen species as suppressors of inflammatory disease

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    Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS-independent activation of NF-kappa B

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    Copyright © 2010 Elsevier B.V. All rights reserved.

    FAQs

    What do neutrophils do in rheumatoid arthritis? ›

    Neutrophils regulate immune and inflammatory response in RA

    Besides secreting proteases, activated neutrophils act like macrophages or dendritic cells in the regulation of adaptive immune response.

    Can rheumatoid arthritis cause high neutrophils? ›

    The association between NLR and disease activity was analyzed. Results: Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and neutrophil counts were significantly higher in RA and AS patients compared to healthy controls.

    Can rheumatoid arthritis cause low neutrophils? ›

    Felty's syndrome is a rare complication of RA, first described in 1924. Its features are low neutrophils (white blood cells) in the blood, infections and leg ulcers in a patient who usually has severe RA.

    Can high neutrophils mean arthritis? ›

    Rheumatoid arthritis. The identification of increased neutrophils in RA synovial fluid, particularly in early disease stages, supports a role for these cells in the pathogenesis of joint destruction [81–85].

    What does it mean if neutrophils are high? ›

    Having a high percentage of neutrophils in your blood is called neutrophilia. This is a sign that your body has an infection. Neutrophilia can point to a number of underlying conditions and factors, including: infection, most likely bacterial.

    What do neutrophils release during inflammation? ›

    Neutrophils respond to multiple signals and respond by producing several cytokines and other inflammatory factors that influence and regulate inflammation and also the immune system (Nauseef and Borregaard, 2014; Scapini and Cassatella, 2014).

    How does RA cause neutropenia? ›

    Autoimmunity with the production of antibodies against granulocytes can cause neutropenia [12]. In patients with RA, the autoimmune process is usually related either to the RA itself or to concomitant Sjögren's syndrome [12], [13].

    What does it mean when neutrophils are low? ›

    Neutropenia is a blood condition characterized by low levels of neutrophils, which are white blood cells that protect your body from infections. Without enough neutrophils, your body can't fight off bacteria. Having neutropenia increases your risk for many types of infection.

    What can cause low neutrophils? ›

    What causes a low neutrophil count? Neutropenia is the result of your body destroying neutrophils before your bone marrow can create more. Causes of a low neutrophil count include: Infection (hepatitis, tuberculosis, sepsis, Lyme disease).

    What does elevated WBC and neutrophils mean? ›

    Neutrophils are a type of white blood cell. They help you fight infection. If there are too many neutrophils in your bloodstream, you may develop leukocytosis, or a high total white blood cell count. You may have symptoms such as fevers or recurring infections. These symptoms may be signs of an underlying condition.

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