Levamisole stimulation of neutrophil chemotaxis and chemokinesis by protection of both the leucoattractant and the cellular chemotactic response from inactivation by the peroxidase/hydrogen peroxide/halide system in vitro.
The effects of levamisole, at concentrations known to stimulate neutrophil motility, on neutrophil post-phagocytic metabolic activity were investigated. Levamisole at these concentrations caused inhibition of hexose monophosphate shunt (HMS) activity, superoxide production, hydrogen peroxide generation and myeloperoxidase (MPO), mediated iodination of ingested Candida albicans,. The inhibition of MPO-mediated iodination was not solely due to lack of H2O availability as a result of decreased HMS activity but also to a primary inhibition of iodination as shown in a cell-free system with horse-radish peroxidase (HRP) and added H2O2 and sodium iodide. Further experiments were designed to investigate possible relationships between stimulation and motility and levamisole-induced inhibition of superoxide generation and peroxidase-mediated iodination. These showed that the peroxidase/halide/H2O2 system caused inactivation of both the leucoattractant and neutrophil chemotactic responsiveness. However, concentrations of levamisole, which stimulate motility and inhibit superoxide production and peroxidase-mediated iodination, protected both the leucoattractant response and the ability of the cell to respond to the leucoattractant from inactivation by the HRP/H2O2/iodide system.
D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006600:Hexosephosphates / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007454:Iodides / Q000494:pharmacology; D007700:Kinetics; D007978:Levamisole / Q000494:pharmacology*; D008715:Methionine / Q000031:analogs & derivatives*; D009239:N-Formylmethionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils; D009842:Oligopeptides / Q000494:pharmacology*; D009195:Peroxidase / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000096:biosynthesis
D006600:Hexosephosphates; D007454:Iodides; D009842:Oligopeptides; D013481:Superoxides; D007978:Levamisole; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008715:Methionine; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D009195:Peroxidase; D013482:Superoxide Dismutase