Activation of macrophages by peroxidases
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Abstract
The role of peroxidase in biological systems is not well understood. The specific aims of the present study were to determine (a) if peroxidases are able to stimulate the production of superoxide by macrophages; (b) if peroxidases are able to activate macrophages to the tumoricidal state; (c) if so, is the cytotoxic triad of peroxidase, HgOg, and a halide ion responsible for promoting such activation; and (d) if simple heme-type compounds can replace peroxidases in promoting such activation.
The results obtained demonstrated that various peroxidases (horseradish peroxidase, lactoperoxidase, microperoxidase) can stimulate both the respiratory burst and promote the inhibition of tumor cell growth by macrophages in a dose-dependent manner. Similar results were obtained using an immobilized peroxidase. The addition of iodide did not markedly affect either process, but the addition of a peroxidase substrate caused a significant increase in the tumoricidal activity of the macrophages. Furthermore, the tumoricidal activity of peroxidase-activated macrophages was inhibited in the presence of cytochrome c, indicating a requirement for superoxide.
Hemin and hematoheme were unable to stimulate either process in macrophages, indicating that the presence of peroxidative activity is a requirement to obtain a stimulation of either process. These results suggest that enzymatically active peroxidases are able to stimulate the respiratory burst as well as induce tumoricidal activity in thioglycollate-induced peritoneal macrophages. The fact that certain compounds, such as interferon, were able to elicit macrophage-mediated tumor cell inhibition without affecting the respiratory burst, suggests that activation of the respiratory burst may not be a prerequisite for tumor cell inhibition. Furthermore, the activation of macrophages is not promoted by the cytotoxic triad, but rather may be promoted by a product of the peroxidative activity of the peroxidases, possibly a free radical species.