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

• Main Authors: Monique P. Gelderman, Rodney Stuart, David Vigerust, Steven Fuhrmann, Doris L. Lefkowitz, Robert C. Allen, Stanley S. Lefkowitz, Susan Graham
• Format: Article
• Language: English
• Published: Hindawi Limited 1998-01-01
• Series: Mediators of Inflammation
• Subjects: Autoimmunity; Peroxidases; TNFα Rheumatoid arthritis; Reactive oxygen intermediates.
• Online Access: http://dx.doi.org/10.1080/09629359890758
• ISSN: 0962-9351; 1466-1861

Rheumatoid arthritis (RA) is characterized by an abnormal cellular and cytokine infiltration of inflamed joints. This study addresses a previously unrecognized interaction between neutrophilic-myeloperoxidase (MPO) and macrophages (MΦ) which could explain the perpetuation of inflammation associated with RA. A monoarticular arthritis was induced in female Lewis rats by injection of streptococcal cell wall extracts (PG-APS). After swelling and erythema subsided, joints were re-injected with one of the following: porcine MPO or partially inactivated MPO (iMPO). Injection with either MPO or iMPO induced a 'flare' of experimental RA. Blocking the MΦ-mannose receptor by mannans, ablated exacerbation of disease. These results indicate that MPO or iMPO can play a pivotal role in the perpetuation but not initiation of this RA model.