Production of angiotensin converting enzyme by rheumatoid synovial membrane

Vascular proliferation and mononuclear cell infiltration are prominent changes observed in synovium from actively inflamed joints of patients with rheumatoid arthritis. Angiotensin converting enzyme (ACE) is a halide activated peptidase produced mainly by endothelial cells and by activated monocytes. It has been proposed that levels of ACE activity in synovial fluid might reflect changes in membrane vascularity, the degree of monocyte infiltration, or the thickness of the lining layer. In this study, ACE activity in serum and synovial fluid samples from 18 patients with inflammatory arthritis was measured and compared with levels in 12 control subjects with non-inflammatory arthritis. Although serum levels were similar in the two groups, ACE activity in synovial fluid was significantly increased in the group with inflammatory arthritis compared with controls (mean (SE) 37 (5) v 19 (3)). Staining of synovial membranes from patients with rheumatoid arthritis with a monoclonal antibody to ACE localised ACE to the endothelium and to mononuclear cells of macrophage origin. ACE activity was then measured in supernatants of synovial membrane from patients with rheumatoid arthritis after one and seven days of culture. A significant increase in ACE activity was observed after seven days of culture (mean (SE) day 1, 17 (5) v day 7, 25 (3)). Levels of ACE activity, however, did not correlate with the lining layer thickness, with the number of macrophages per square millimetre, nor with the number of blood vessels per square millimetre of synovial tissue. No correlation was observed either between levels of ACE in the supernatant of synovial membrane and levels of interleukin 1 or interleukin 6. In conclusion, ACE is produced by the synovial membrane of patients with rheumatoid arthritis and is localised to monocytes and endothelial cells. Levels of activity do not directly reflect membrane vascularity, monocyte or macrophage number, or the thickness of the lining layer.