PRODUCTION OF NITRIC-OXIDE IN THE SYNOVIAL-MEMBRANE OF RHEUMATOID ANDOSTEOARTHRITIS PATIENTS

We have demonstrated spontaneous nitric oxide (NO) production by prima ry synovial cultures from rheumatoid (RA) and osteoarthritis patients. Increased NO production followed addition of staphylococcal enterotox in B. Immunochemical double staining with specific anti-human inducibl e NO synthase (iNOS) and nonspecific esterase (NSE), or anti-CD68 (mar kers for tissue macrophages) showed that although many lining layer ce lls in RA synovium expressed iNOS, most (similar to 90%) were NSE(-) a nd CD68(-), with only a minor population (similar to 10%) which were i NOS(+), CD68(+)/NSE(+). These data demonstrate the capacity for high o utput of NO by human synovial tissue and show that, although human mac rophages can express high levels of iNOS, the majority of cells expres sing iNOS are fibroblasts. We also report that synoviocytes, and macro phage cell lines, cultured with the NO donor, S-nitroso-acetyl penicil lamine, produced high concentrations of tumor necrosis factor (TNF)-al pha. These results suggest that NO may mediate pathology in RA through the induction of TNF-alpha production.