HUMAN EOSINOPHIL PEROXIDASE ENHANCES TUMOR-NECROSIS-FACTOR AND HYDROGEN-PEROXIDE RELEASE BY HUMAN MONOCYTE-DERIVED MACROPHAGES

Inhibition of growth or eradication of experimentally induced tumors h as been shown to be accompanied by infiltration of eosinophiis and mac rophages into the tumor mass. Since macrophages are important mediator s of host antitumor activity, the possibility arises that a collaborat ion may exist between these two cell types in the control of tumor gro wth. In this study, we report the effect of eosinophiI peroxidase (EPO ), a basic protein contained in eosinophils that binds to several cell types including macrophages, on tumor necrosis factor (TNF) productio n and hydrogen peroxide release by human monocyte-derived macrophages. After incubation with EPO, the macrophages produced large amounts of TNF and displayed an enhanced phorbol 12-myristate 13-acetate-triggere d hydrogen peroxide release. These effects were accompanied by an incr eased cell protein content and by morphologic changes leading the larg e, round macrophages of the control cultures to become elongated, pear -like or spindle shaped cells after treatment with EPO. The stimulator y effect of EPO on hydrogen peroxide release was insensitive to additi on of exogenous catalase, a HzOa-degrading enzyme, suggesting that an extracellular catalytic activity of EPO was not involved. In addition, myeloperoxidase, the homologous peroxidase of neutrophils with a cata lytic activity similar to that of EPO, was ineffective. The EPO-induce d effects differed in several aspects from the effects of lipopolysacc aride and interferon-y, two well-known macrophage activators. These fi ndings provide supportive evidence for a functional interrelationship between eosinophils and macrophages that may be physiologically releva nt in the tumoricidal activity of macrophages.