H2O2-generating lactobacilli (LB+) are present in the vagina of most normal women but are absent from most women with bacterial vaginosis (BV). LB+ at high concentration was toxic to Gardnerella vaginalis (the predominant organism in the vagina of women with BV); when the LB+ was lowered to a level where it was ineffective alone, the addition of myeloperoxidase and chloride reinstituted toxicity. Toxicity was inhibited by catalase and was not seen when H2O2-negative lactobacilli were used, implicating H2O2 as the toxic molecule. LB+ could be replaced by H2O2 and chloride by iodide, bromide, or thiocyanate. The optimum pH for inhibition of G. vaginalis was 5.0-6.0 LB+ also was autoinhibitory when combined with myeloperoxidase and chloride. LB+ alone at low concentrations was toxic to Bacteroides bivius through the formation of H2O2. Adequate amounts of peroxidase were found in the vagina of 17 of 21 women. These findings suggest that LB+ may contribute to the control of the vaginal flora, particularly in the presence of peroxidase and a halide.

A purified recombinant human granulocyte-macrophage colony stimulating factor (rH GM-CSF) was a powerful stimulator of mature human eosinophils and neutrophils. The purified rH GM-CSF enhanced the cytotoxic activity of neutrophils and eosinophils against antibody-coated targets, stimulated phagocytosis of serum-opsonized yeast by both cell types in a dose-dependent manner, and stimulated neutrophil-mediated iodination in the presence of zymosan. In addition, rH GM-CSF enhanced Nformylmethionylleucylphenylalanine(FMLP)-stimulated degranulation ofCytochalasin B pretreated neutrophils and FMLPstimulated superoxide production. In contrast, rH GM-CSF did not promote adherence of granulocytes to endothelial cells or plastic surfaces. rH GM-CSF selectively enhanced the surface expression of granulocyte functional antigens 1 and 2, and the Mol antigen. rH GM-CSF induced morphological changes and enhanced the survival of both neutrophils and eosinophils by 6 and 9 h, respectively. These experiments show that granulocytemacrophage colony stimulating factor can selectively stimulate mature granulocyte function.

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Oxygen free radicals are highly reactive species generated by many cellular oxidation-reduction processes. These radicals damage cellular constituents and have been causally implicated in the pathogenesis of many human diseases. We report here that oxygen free radicals generated by Fe2+ in aqueous solution are mutagenic. Aerobic incubation of 4X174 am3 (amber 3 mutation) DNA with Fe2+ results in decreased phage survival when the treated DNA is transfected into Escherichia coli spheroplasts. Transfection of the treated DNA into SOS-induced spheroplasts results in an increase in mutagenesis as great as 50-fold. Both killing and mutagenesis can be prevented by binding of Fe2+ with deferoxamine or by the addition of catalase or mannitol. These results suggest that DNA damage and mutagenesis brought about by Fe2+ are likely to occur by a Fenton-type mechanism that involves the generation of (i) hydrogen peroxide by the autoxidation of iron and (ii) hydroxyl radicals by the interaction of the hydrogen peroxide with Fe2+. DNA sequence analysis of the Fe2+-induced mutants indicates that reversion of the phage phenotype to wild type occurs largely by a transversion type of mutation involving substitution of deoxyadenosine for thymidine opposite a template deoxyadenosine. Mutagenesis is not abolished by incubation of Fe22+-treated 4X174 am3 DNA with an apurinic endonuclease and only partially abolished by incubation with alkali, suggesting that a large fraction of the mutagenesis by oxygen free radicals is not caused by formation of apurinic sites but instead involves an as-yet-to-be-defined alteration in deoxyadenosine. These fmdings raise the possibility that free iron localized in cellular DNA may cause mutations by the generation of oxygen free radicals.A portion of the total cellular oxygen metabolism proceeds by a sequence of one-electron reductions that result in oxygen free-radical intermediates. Processes reported to yield oxygen free radicals include phagocytosis, ischemic cell injury, and drug toxicity (1-4). The resultant free radicals have been hypothesized to be causative factors in aging (5), carcinogenesis (5, 6), and radiation injury (7) and to be a contributory factor in tumor promotion (8)(9)(10) with the overall reaction being the iron-catalyzed interaction between 02 and H202 to form OH-or a similarly reactive species (Haber-Weiss reaction):

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