MAST-CELL ACTIVATION IN ARTHRITIS - DETECTION OF ALPHA-TRYPTASE AND BETA-TRYPTASE, HISTAMINE AND EOSINOPHIL CATIONIC PROTEIN IN SYNOVIAL-FLUID

1. Although mast cell hyperplasia is a feature of rheumatoid arthritis and osteoarthritis, the extent and nature of mast cell activation in joint disease have not been clearly established. 2. We have investigat ed the levels of mast cell tryptase and histamine and also of eosinoph il cationic protein in synovial fluid collected from 31 patients with rheumatoid arthritis, 14 with seronegative spondyloarthritis and nine with osteoarthritis. live RIAs for tryptase were employed: one with mo noclonal antibody AA5, which was found to bind equally well to both al pha and beta isoforms on Western blots of the recombinant enzyme, and the other with antibody G5, which recognizes predominantly beta-trypta se. 3. alpha-Tryptase, which is likely to be released constitutively f rom mast cells, appeared to be the major form in synovial fluid, as th e assay with antibody AA5 detected appreciably more tryptase than that with antibody G5. beta-Tryptase, which is released on anaphylactic ac tivation of mast cells, was detected in 14 out of 45 synovial fluid sa mples studied, with concentrations of up to 12 mu g/l measured by the G5 assay. The apparent levels of beta-tryptase, but not of alpha-trypt ase, were closely correlated with those of histamine in the synovial f luid. Patients with osteoarthritis appeared to have a greater proporti on of beta-tryptase in the synovial fluid than those with rheumatoid a rthritis, as well as higher concentrations of histamine. Eosinophil ca tionic protein was present at high levels in the synovial fluid, altho ugh eosinophil numbers were low, and its concentrations were not corre lated with the concentrations of the mast cell products. 4. These data suggest that anaphylactic degranulation of mast cells may have occurr ed to a greater extent in osteoarthritis than in rheumatoid arthritis, despite the relative lack of synovial inflammation in osteoarthritis. Although the eosinophil cationic protein detected may not reflect eos inophilic inflammation in the joint, the presence in synovial fluid of tryptase of both major forms, and of histamine, appears to indicate t hat mast cell products are secreted constitutively, as well as by proc esses of anaphylactic degranulation in rheumatoid arthritis, seronegat ive spondyloarthritis and osteoarthritis.