Email updates

Keep up to date with the latest news and content from Journal of Inflammation and BioMed Central.

Open Access Research

Cross-linking of IgGs bound on circulating neutrophils leads to an activation of endothelial cells: possible role of rheumatoid factors in rheumatoid arthritis-associated vascular dysfunction

Emmanuelle Rollet-Labelle1*, Myriam Vaillancourt1, Louis Marois1, Marianna M Newkirk3, Patrice E Poubelle2 and Paul H Naccache1

Author Affiliations

1 Centre de recherche en rhumatologie et immunologie, Centre de recherche du CHU de Québec, Département de Microbiologie-Infectiologie et Immunologie, Faculté de médecine, Université Laval, Québec, QC, Canada

2 Centre de recherche en rhumatologie et immunologie, Centre de recherche du CHU de Québec Département de Médecine, Faculté de médecine, Université Laval, Québec, QC, Canada

3 Department of Medicine, Division of Rheumatology, Research Institute of McGill University Health Centre, McGill University, Montreal, QC, Canada

For all author emails, please log on.

Journal of Inflammation 2013, 10:27  doi:10.1186/1476-9255-10-27

Published: 31 July 2013

Abstract

Background

Rheumatoid arthritis is characterized by the presence of circulating auto-antibodies, including rheumatoid factors, which recognize the Fc portion of IgGs. The neutrophil is the most abundant circulating leukocyte and it expresses high levels of FcγRs on its surface. The aim of the present study was to examine the capacity of circulating human neutrophils to be activated by rheumatoid factors and the consequences of these events on endothelium.

Methods

Neutrophil-bound IgGs were cross-linked with anti-human IgGs to mimick the presence of circulating rheumatoid factors and FcγRs-dependent signalling events and functions were examined. The IgG and IgM composition of rheumatoid factors isolated from the serum of RA patients was characterized. Adhesion of neutrophils to endothelial cells was quantified in response to the addition of rheumatoid factors.

Results

Cross-linking of IgGs bound on neutrophils leads to FcγRs-dependent tyrosine phosphorylation, mobilisation of intracellular calcium and the extracellular release of superoxide anions and lysozyme. Incubation of endothelial cells with the supernatant of activated neutrophils increases ICAM-1 expression and IL-8 production by endothelial cells. Finally, rheumatoid factors enhance neutrophil adhesion to endothelial cells.

Conclusions

Our results show that activation of neutrophils’ FcγRs by rheumatoid factors could participate in rheumatoid arthritis-associated vascular damage.

Keywords:
Rheumatoid factors; Human neutrophils; FcγRs; Endothelial cells; Vascular damage