Perpetuation of inflammation associated with experimental arthritis: the role of macrophage activation by neutrophilic myeloperoxidase

RHEUMATOID arthritis (RA) is characterized by an abnormal cellular and cyto kine infiltration of inflamed joints. This study addresses a previously unr ecognized interaction between neutrophilic-myeloperoxidase (MPO) and macrop hages (Mo) which could explain the perpetuation of inflammation associated with RA. A monoarticular arthritis was induced in female Lewis rats by inje ction of streptococcal cell wall extracts (PG-APS). After swelling and eryt hema subsided, joints were re-injected with one of the following: porcine M PO or partially inactivated MPO (iMPO). injection with either MPO or iMPO i nduced a 'flare' of experimental RA. Blocking the Mpr-mannose receptor by m annans, ablated exacerbation of disease. These results indicate that MPO or iMPO can play a pivotal role in the perpetuation but not initiation of thi s RA model.