Involvement of Reactive Oxygen Metabolites in the Candidacidal Activity of Human Neutrophils Stimulated by Muramyl Dipeptide or Tumor Necrosis Factor

• Published in: Immunobiology (1979) 1989-11, Vol.180 (1), p.68-79
• Main Authors: Jupin, Claude, Parant, Monique, Chedid, Louis
• Format: Article
• Language: English
• Subjects: Acetylmuramyl-Alanyl-Isoglutamine - pharmacology; Biological and medical sciences; Candida albicans - immunology; Cells, Cultured; Cytochalasin B - pharmacology; Cytochrome c Group - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Myeloid cells: ontogeny, maturation, markers, receptors; Neutrophils - immunology; Neutrophils - metabolism; Nitroblue Tetrazolium - metabolism; Oxygen - metabolism; Phagocytosis; Recombinant Proteins; Saccharomyces cerevisiae - metabolism; Superoxide Dismutase - pharmacology; Tetradecanoylphorbol Acetate - pharmacology; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/S0171-2985(89)80031-2

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 μg/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 0 - 2 anion for intracellular killing. Cytochalasin B abrogated the PMN fungicidal potency in all cases.