Rheumatoid peripheral blood phagocytes are primed for activation but have impaired Fc-mediated generation of reactive oxygen species
Open Access
- 13 March 2007
- journal article
- Published by Springer Nature in Arthritis Research & Therapy
- Vol. 9 (2), R29
- https://doi.org/10.1186/ar2144
Abstract
Significant levels of circulating immune complexes (ICs) containing rheumatoid factors and immunoglobulin G in peripheral blood are a characteristic feature of rheumatoid arthritis (RA). ICs interact through Fcγ receptors (FcγR) to activate phagocytes in numerous inflammatory processes. The high concentration of neutrophils in synovial fluid during active phases of the disease, together with their destructive capacity, pose important questions as to their role in the pathogenesis of RA. Functional defects in RA or control peripheral blood neutrophil FcγRs were examined with a specific FcγR-mediated reactive oxygen species (ROS) assay. Heterologous cross-linking of FcγRIIa and FcγRIIIb on neutrophils resulted in a significantly decreased production of ROS by RA cells compared with controls matched for age and sex. However, expression and homologous ligation of receptors did not differ between these groups. These data suggest that neutrophil priming does occur before emigration into the joint and that blood neutrophils from patients with RA have a functional impairment in cooperative FcγR-mediated ROS generation. This may account for the increased susceptibility to bacterial infection that arises in patients with severe disease.Keywords
This publication has 71 references indexed in Scilit:
- Essential Role of Neutrophils in the Initiation and Progression of a Murine Model of Rheumatoid ArthritisThe Journal of Immunology, 2001
- DIVERGENT ROLES FOR FcRECEPTORS AND COMPLEMENT IN VIVOAnnual Review of Immunology, 1998
- Seeing the wood for the trees: the forgotten role of neutrophils in rheumatoid arthritisImmunology Today, 1997
- Clinical significance of IgG Fc receptors and FcγR-directed immunotherapiesImmunology Today, 1997
- Fc receptorsCurrent Opinion in Immunology, 1997
- THE NEUTROPHIL IN RHEUMATOID ARTHRITISRheumatic Disease Clinics of North America, 1995
- Activation of neutrophil reactive-oxidant production by synovial fluid from patients with inflammatory joint disease. Soluble and insoluble immunoglobulin aggregates activate different pathways in primed and unprimed cellsBiochemical Journal, 1992
- The prostaglandin paradox: additive inhibition of neutrophil function by aspirin-like drugs and the prostaglandin E1 analog misoprostol.1991
- Cytotoxicity mediated by human Fc receptors for IgGImmunology Today, 1989
- Induction of neutrophil enzyme release by rheumatoid factors: Evidence for differences based on molecular characteristicsClinical Immunology and Immunopathology, 1986