Fcγ and Complement Receptors and Complement Proteins in Neutrophil Activation in Rheumatoid Arthritis: Contribution to Pathogenesis and Progression and Modulation by Natural Products.
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.
Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida Café s/n, 14040-903 Ribeirão Preto, SP, Brazil ; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Adriana Balbina
AB
Paoliello-Paschoalato
Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
Larissa Fávaro
LF
Marchi
Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida Café s/n, 14040-903 Ribeirão Preto, SP, Brazil ; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Micássio Fernandes
MF
de Andrade
Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
Luciana Mariko
LM
Kabeya
Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Eduardo Antônio
EA
Donadi
Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
Yara Maria
YM
Lucisano-Valim