title: Involvement of reactive oxygen metabolites in the candidacidal activity of human neutrophils stimulated by muramyl dipeptide or tumor necrosis factor.
abstract: In the presence of the adjuvant glycopeptide muramyl dipeptide (MDP), purified human PMN exhibited an enhanced capacity to kill Candida albicans cells at various cell ratios. A significant effect was obtained at 100 ng/ml MDP, and the maximum was reached at 1 micrograms/ml MDP. Recombinant human tumor necrosis factor (rHuTNF), a monokine that enhances host resistance to bacterial and fungal infections, also stimulated the candidacidal potency of PMN with a maximal effect at 10(-2) ng/ml rHuTNF. When MDP- or rHuTNF-stimulated PMN were cultured with yeast cells, the intracellular production of oxygen metabolites was enhanced. Pretreatment with inhibitors of oxidative burst demonstrated that the yeast cell killing by MDP-stimulated PMN was not affected by SOD but was inhibited by sodium azide, indicating the involvement of myeloperoxidase (MPO)-halide system in fungicidal mechanisms induced by MDP. When PMN were stimulated with rHuTNF, the killing of yeast cells was neutralized by iodoacetamide, showing that the candidacidal potency of stimulated-PMN was due to oxygen derivatives. Inhibition by sodium azide and sodium benzoate indicated that these oxygen metabolites could be derived from the MPO-halide system but also from hydroxyl radical production. Moreover, SOD partially inhibited the fungicidal potency of rHuTNF-stimulated PMN, thus indicating a possible reutilization of the released O2- anion for intracellular killing. Cytochalasin B abrogated the PMN fungicidal potency in all cases.
authors.affiliation: Immunopharmacologie Expérimentale, Institut Biomédical des Cordeliers, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Jupin
authors.forename: M
authors.initials: M
authors.lastname: Parant
authors.forename: L
authors.initials: L
authors.lastname: Chedid
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D002176:Candida albicans / Q000276:immunology*; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010587:Phagocytosis; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D003574:Cytochrome c Group; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009580:Nitroblue Tetrazolium; D003571:Cytochalasin B; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen