Expression of vascular endothelial growth factor by synovial fluid neutrophils in rheumatoid arthritis (RA)

Most of the leucocytes infiltrating rheumatoid synovial fluid (SF) are neutrophils capable of producing a variety of inflammatory mediators known to contribute significantly to the disease process during active RA. In the present study, we investigated the contribution made by SF neutrophils to the elevated levels of vascular endothelial growth factor (VEGF) seen in rheumatoid SF. Rheumatoid SF neutrophils were found to contain significantly larger amounts of both VEGF protein and its mRNA than peripheral blood neutrophils from either RA patients or healthy controls. Levels of cell-associated VEGF were well correlated with free VEGF in SF, which was significantly higher than in SF from osteoarthritis patients. Levels of SF neutrophil-associated VEGF also correlated with RA disease activity and cell surface integrin expression. Thus, SF neutrophil-associated VEGF may be considered an indicator of both local and systemic inflammation of RA, contributing to the neovascularization seen during RA synovitis.