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

Abstract

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.

Regulation of B-cell-activating factor (BAFF)/B lymphocyte stimulator (BLyS) expression in human neutrophils

“…Whatever the case may be, the observations made above, together with those indicating that SF neutrophils from RA patients express significantly lower mBAFF/BLyS levels than peripheral blood neutrophils [25], strongly support the view that inflammatory neutrophils, in addition to monocytes, contribute to augment sBAFF/BLyS accumulation in inflammatory fluids of the rheumatoid joints [34]. This view is also in agreement with the fact that neutrophils isolated from synovial fluids have been shown to produce abnormal levels of many other cytokines, including interleukin-1 (IL-1), IL-1ra, vascular endothelial growth factor (VEGF), CXCL1, CXCL8, and transforming growth factor-␤1 (TGF␤1), when compared with peripheral blood neutrophils [23,35]. Thus, it is tempting to speculate that sBAFF/BLyS overproduction by neutrophils might play a crucial role not only in the pathogenesis of autoimmune disorders (such as RA itself), but also in other chronic inflammatory conditions or infectious diseases in which concentrations of either G-CSF or TNF␣ are elevated [36][37][38], or even in haematological diseases involving a dysregulation of B-cell homeostasis [39].…”

Mice Transgenic for IL-1 Receptor Antagonist Protein Are Resistant to Herpetic Stromal Keratitis: Possible Role for IL-1 in Herpetic Stromal Keratitis Pathogenesis

“…Thus, in line with the minimal early PMN response noted in IL-1ra Tg mice, such animals showed a marked reduction in angiogenesis compared with controls. One factor derived from PMN, as well as from other cell types involved in neovascularization, is VEGF (33,34). We demonstrated that VEGF was significantly down-regulated in IL-1ra Tg mice in comparison with control animals.…”

Antiangiogenesis for Rheumatoid Arthritis

“…In RA patients, VEGF is produced by macrophages, fibroblasts surrounding microvessels, vascular smooth muscle cells, synovial lining cells [17], neutrophils of synovial fluid [18], and peripheral blood mononuclear cells [19]. Its levels are significantly higher in synovial fluids from RA as compared with OA [20][21][22].…”