Immunomodulation of macrophage function by recombinant human myeloperoxidase
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Regulation of the immune response is necessary for protection of the host as well as the avoidance of autoimmune diseases. The regulation of macrophage function by myeloperoxidase is a previously unrecognized function of this enzyme. A recombinant form of myeloperoxidase, an enzyme commonly found in neutrophils, was used to study the effects of this enzyme on certain macrophage capacities and functions. Both neutrophils and macrophages are present at the site of either inflammation or infection. Stimulation of macrophages by pathogens such as bacteria and fungi, results in production of reactive oxygen intermediates. This study showed that myeloperoxidase induced the production of these reactive oxygen intermediates. Myeloperoxidase was shown to increase the uptake and subsequent killing of a common fungal pathogen, Candida albicans, demonstrating its ability to alter the macrophage response. In addition, these same intermediates act on surrounding tissue and cause damage observed with diseases such as rheumatoid arthritis. The interaction of myeloperoxidase and macrophages at the site of inflanunation could result in the observed chronic inflammatory state seen in rheumatoid arthritis patients. Studies by other investigators have detected myeloperoxidase in the synovial fluids of patients with rheumatoid arthritis. Evidence for the establishment of macrophage-mediated chronic inflammation was provided by studies demonstrating the de novo synthesis and secretion of cytokines by macrophages after exposure to myeloperoxidase. The production of macrophage-derived cytokines, which are powerful mediators of inflammation as well as the immune system, provides further evidence for the macrophage myeloperoxidase interaction in chronic inflanmiation. The role of myeloperoxidase in mediating the immune response, both in a protective function as well as a potentially destructive role, is novel in the study of chronic inflammation.