Infiltration of the synovium by mononuclear cells, namely lymphocytes and monocytes, is one of the main features of rheumatoid arthritis (RA) and is considered to be responsible for the development of the disease. In this study in 31 consecutive patients with RA, we investigated whether peripheral blood monocytes exhibited markers of cellular activation related to cell migration. Using flow cytometry with the respective specific antibodies, we studied the expression of integrins CD11a, CD11b, CD11c, CD49d (VLA‐4), and CD49e (VLA‐5) on monocytes from patients with RA and from normal (N) subjects. IL‐1β, IL‐6, and tumour necrosis factor‐alpha (TNF‐α) production by cultured monocytes was measured by immunoassay. Adhesiveness of monocytes was studied on various surfaces (plastic, human fibronectin, gelatin‐coated plasma, subendothelial matrix) and on cultured endothelial cells under basal conditions or after stimulation by IL‐1β. An increased number of CD14+ monocytes (Mo) from RA patients expressed the CD11b molecule (RA Mo = 90.3%, N Mo = 83.4%, P < 0.005). The expression of CD11b on CD14+ monocytes was significantly increased in RA patients (median fluorescence intensity (FI): RA Mo = 145 (range 80–466) units; normal Mo = 95 (range 24–164) units; P < 0.003). Production of extracellular IL‐1β and IL‐6 by RA monocytes was significantly enhanced compared with monocytes from normal subjects (IL‐1β : RA = 2.65 ± 0.91 ng/ml versusN = 1.35 ± 0.85 pg/ml, P < 0.05; IL‐6: RA = 4.83 ± 0.90 ng/ml versusN = 2.40 ± 0.95 ng/ml, P < 0.05). Compared with normal monocytes, RA monocytes exhibited increased adhesion to the various surfaces studied (plastic, P < 0.01; fibronectin, P < 0.01; and gelatin‐coated normal or RA plasma, P < 0.01) as well as to unstimulated (P < 0.01) and IL‐1β‐stimulated endothelial cells (IL‐1β for 4 h, P < 0.05; IL‐1β for 24 h, P < 0.05). In our study, blood monocytes from RA patients exhibited features of activation related to cell adhesion.

SUMMARYAngiogenesis is a key process in the pathogenesis of inflammatory arthritis. Angiogenin is one of the most potent inducers of neovascularization in experimental models in vivo . To look for evidence that angiogenin is involved in inflammatory joint disease, we examined plasma and synovial fluid (SF) samples from rheumatology patients and synovial fibroblast cell culture supernatants. Angiogenin levels were determined by radioimmunoassay and ELISA. Plasma angiogenin concentrations ranged from 96 to 478 ng/ml, with no significant difference between patients and normal controls. In SF, angiogenin concentrations were significantly higher in patients with acute or chronic synovitis (rheumatoid arthritis (RA): median, 104 ng/ml; range 13-748, n = 14; crystal-induced arthritis (CIA): median, 149 ng/ml; range, 37-616, n = 14, and other chronic inflammatory arthritis: median, 42 ng/ml; range, 15-205; n = 9) than in the 18 patients with osteoarthritis (OA) (median, 20 ng/ml; range 8-116) ( P < 0·0001, ANOVA ). Angiogenin levels in SF from RA patients in remission with secondary OA were similar to those achieved in primary OA, and decreased in parallel with the resolution of acute gout. Angiogenin protein was released by cultured synovial fibroblasts from OA and RA patients, and reached 1·18 ng/10 6 cells/ day. These data suggest that angiogenin may mediate local inflammation in arthritis via effects on angiogenesis and leucocyte regulation.

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