Neutrophil microbicidal activity is a consequence of overlapping antimicrobial systems that vary in prominence according to the conditions of the neutrophil-microbe interaction, the nature of the microbe, and its metabolic state. In this study, normal,
myeloperoxidase-deficient, and respiratory burst-deficient (
chronic granulomatous disease [CGD]) neutrophils killed Escherichia coli with equivalent, high efficiencies. Killing by CGD and
myeloperoxidase-deficient neutrophils was not augmented by supplements, such as exogenous H2O2 and
myeloperoxidase, directed at ameliorating their metabolic defects, suggesting that nonoxidative microbicidal systems were sufficient for a full microbicidal effect. Neutrophils with an intact
myeloperoxidase antimicrobial system (normal or appropriately supplemented deficient cells) were capable of rapidly suppressing E. coli
DNA synthesis, while unsupplemented CGD or
myeloperoxidase-deficient cells were far less effective, indicating that the
myeloperoxidase system was active in normal neutrophils. The degree of
DNA synthesis inhibition by
myeloperoxidase-sufficient neutrophils could account, in a cell-free system, for most of the observed microbicidal activity. While the
myeloperoxidase system was active and probably bactericidal, it was not rate limiting for microbicidal activity and appears to have been redundant with other microbicidal systems in the cell. Rapid and extensive inhibition of
bacterial DNA synthesis appears to be an
indicator of
myeloperoxidase activity in neutrophils.