OXIDATIVE MECHANISMS UTILIZED BY HUMAN-NEUTROPHILS TO DESTROY ESCHERICHIA-COLI

  • 1 January 1984
    • journal article
    • research article
    • Vol. 63  (6) , 1361-1368
Abstract
Serum-opsonized bacteria are efficiently ingested and killed by neutrophils within the phagocytic vacuole, where they are exposed to an array of reactive O2 metabolites and toxic lysosomal components. Although bacteria may be destroyed by O2-independent mechanisms alone, many types of bacteria are not killed effectively unless they are attacked by O2 metabolites. The apparent inability of extracellular scavengers, or inhibitors, of O2 metabolites to gain access to the phagocytic vacuole makes this system difficult to evaluate. The ability of neutrophils triggered with phorbol myristate acetate to destroy unopsonized E. coli was examined in a serum-free model system. Neutrophils incubated with phorbol myristate acetate at a cell-to-bacteria ratio of 1:4 caused a > 95% reduction in colony-forming units (CFU) of E. coli in 60 min at 37.degree. C. Destruction of E. coli by the stimulated neutrophils was dependent on neutrophil number, stimuli concentration, and the incubation period. The neutrophil-mediated bactericidal effect was stimulated by superoxide dismutase, but was inhibited by catalase, azide or compounds known to scavenge hypochlorous acid. Although stimulated neutrophils can generate long-lived endogenous N-chloroamines, these compounds did not play a direct role in destruction of E. coli in the model system. In the presence of exogenous iodide, endogenous N-chloroamines exerted a powerful bactericidal effect. Neutrophils triggered with opsonized zymosan could also mediate E. coli destruction by a qualitatively similar process. Neutrophils apparently have the potential to utilize the myeloperoxidase system to generate bactericidal quantities of a species with characteristics similar to, if not identical with, hypochlorous acid.

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