Secretion of Oxygen Intermediates: Role in Effector Functions of Activated Macrophages

The ability of macrophages to secrete reactive oxygen intermediates, such as superoxide or hydrogen peroxide, correlates closely with their capacity to kill trypanosoma, toxoplasma, leishmania, and candida. In this sense, secretion of oxygen intermediates is a biochemical marker of macrophage activation. The close correlation between oxidative metabolism and antimicrobial activity appears to stem from the direct involvement of oxygen intermediates in the killing of the same parasites by the macrophages. Similarly, there seem to be at least three experimental settings in which oxygen intermediates play a major role in nonphagocytic lysis of tumor cells by macrophages: in the presence of phorbol myristate acetate, of antitumor antibody, or of a peroxidase derived from eosinophils. These findings direct attention to antioxidant defenses in tumor cells and parasites. The oxidation-reduction cycle of glutathione is one major pathway used by tumor cells to limit oxidative injury by macrophages and granulocytes. Thus, cytotoxicity is augmented by inhibition of glutathione reductase or glutathione peroxidase, by interruption of glutathione synthesis, or by diversion of glutathione into another pathway. On the other hand, catalase appears to play a prominent role in limiting macrophage effector function against toxoplasma.