SOLUBLE OLIGONUCLEOSOMAL COMPLEXES IN SYNOVIAL-FLUID FROM INFLAMED JOINTS

Objective. To determine whether soluble oligonucleosomal DNA, typical of that released during apoptotic cell death, is present in synovial f luids from inflamed joints and, if so, whether it is present in suffic ient concentrations to have pathophysiologic significance. Methods. Fi fty synovial fluid specimens from 46 patients were studied, 41 from jo ints with a variety of inflammatory disorders and 9 from osteoarthriti c joints, DNA from freshly collected synovial fluid was isolated and q uantitated by microfluorometry, and the oligonucleosomal fraction was measured by radiolabeling, gel electrophoresis, and autoradiography, S pecific immunoprecipitation with monoclonal antihistone antibody, afte r DNA radiolabeling in whole synovial fluid, was used to detect histon e binding. Results. DNA with a typical oligonucleosomal ladder was obs erved in most specimens, The mean +/- SD oligonucleosomal DNA concentr ation was 14.1 +/- 18.5 mu g/ml in synovial fluids from inflamed joint s, considerably higher than that in osteoarthritic synovial fluids, Ad ditionally, the DNA was shown to be complexed with histone, as would b e expected, Control experiments were performed to show that the oligon ucleosomal DNA was present in soluble form and did not arise due to in vitro artifact, The DNA concentrations were found to correlate signif icantly with the concentrations of synovial fluid leukocytes, most of which were neutrophils. Conclusion. Synovial fluids from inflamed join ts contain oligonucleosomal DNA typical of that released during apopto tic cell death. The probable source is fluid-phase neutrophils undergo ing apoptotic cell death, although this was not directly demonstrated. The concentrations are sufficient to have biologic activity similar t o that shown in vitro, including lymphoproliferation and stimulation o f interleukin-6 secretion, A mechanism by which oligonucleosomal DNA m ay contribute to perpetuation of rheumatoid synovitis is proposed, If it is generalizable to other sites of inflammation, as seems probable, similar oligonucleosomal DNA release accompanying inflammation may pl ay a pathogenetic role in other disorders, including systemic lupus er ythematosus.