Abstract
Rheumatoid arthritis (RA) is a highly disabling disease that affects all structures of the joint and significantly impacts on morbidity and mortality in RA patients. RA is characterized by persistent inflammation of the synovial membrane lining the joint associated with infiltration of immune cells. Eighty to 90% of the leukocytes infiltrating the synovia are neutrophils. The specific role that neutrophils play in the onset of RA is not clear, but recent studies have evidenced that they have an important participation in joint damage and disease progression through the release of proteolytic enzymes, reactive oxygen species (ROS), cytokines, and neutrophil extracellular traps, in particular during frustrated phagocytosis of immune complexes (ICs). In addition, the local and systemic activation of the complement system contributes to the pathogenesis of RA and other IC-mediated diseases. This review discusses (i) the participation of Fcγ and complement receptors in mediating the effector functions of neutrophils in RA; (ii) the contribution of the complement system and ROS-dependent and ROS-independent mechanisms to joint damage in RA; and (iii) the use of plant extracts, dietary compounds, and isolated natural compounds in the treatment of RA, focusing on modulation of the effector functions of neutrophils and the complement system activity and/or activation.
Highlights
Rheumatoid arthritis (RA) occurs in 0.5–1.0% of the adult population worldwide and accounts for around 250,000 hospitalizations and 9 million doctor visits per year [1]
Given the importance of immune complexes (ICs) deposited in the RA patients’ synovia to elicit the effector functions of neutrophils via Fcγ and complement receptors (FcγR and CR, resp.), the present paper aims to discuss the participation of these receptors and complement proteins in the production of reactive oxygen species (ROS) and release of granule components by neutrophils in the inflamed synovia and in peripheral blood
Contrary to the traditional view that high levels of ROS mediate inflammation, some researchers argue that reduction in ROS production capacity due to polymorphisms in the respiratory burst component neutrophil cytosolic factor 1 (Ncf1 or p47phox) gene promotes the activation of arthritogenic T cells and leads to severe arthritis in rodents [111, 112]
Summary
Rheumatoid arthritis (RA) occurs in 0.5–1.0% of the adult population worldwide and accounts for around 250,000 hospitalizations and 9 million doctor visits per year [1]. RA is characterized by synovial hyperplasia, swelling, pain, and neutrophil-rich infiltrates and can lead to bone erosion, cartilage destruction, and complete loss of joint integrity over time This condition is classified as an autoimmune disorder because it involves the formation of antibodies against selfantigens causing immune complex (IC) deposits in synovial tissue of patients with RA [3, 4]. The rheumatoid factors—which are autoantibodies directed to the Fc fraction of immunoglobulin G (IgG)—and anti-CCP antibodies can be detected in the preclinical phase of the disease. The levels of these antibodies tend to increase as a function of the age at diagnosis of RA [9]. This paper discusses the future perspectives in the treatment of RA patients with plant extracts, dietary compounds, and isolated natural compounds to minimize the harmful effects of the overactivation of neutrophils and the complement system
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