Neutrophilic myeloperoxidase-macrophage interactions perpetuate chronic inflammation associated with experimental arthritis

Rheumatoid arthritis is a systemic disease of unknown etiology. The purpose of this stud was to elucidate an unrecognized interaction between neutroph ilic myeloperoxidase (MPO) and macrophages (M phi) which could perpetuate t he inflammatory response associated with arthritis. A monoarticular arthrit is was induced by intra-articular injection of group A streptococcus cell w all fragments (PG-APS) into the ankle joint of female Lewis rats. After swe lling/erythema subsided, joints were reinjected with either recombinant MPO or enzymatically inactive MPO (iMPO). Joint measurements were made daily a nd arthritis was confirmed by histology. Neither iMPO nor MPO could initiat e "clinical" arthritis, however, either form of the enzyme injected after P G-APS induced a dose-independent increase in erythema and swelling. Mannans , which bloc the binding of MPO to Mo, ablated clinical symptoms. Also, the presence of tumor necrosis factor alpha was observed only in diseased join ts using immunocytochemistry. (C) 1999 Academic Press.