Inhibitory effect of antibiotic cerulenin on the respiratory burst in phagocytes. II. Inhibition by cerulenin of intracellular calcium mobilization in human neutrophils.
Generation of superoxide anion (O2-) and mobilization of intracellular Ca2+ in human neutrophils upon exposure to stimuli such as N-formylmethionylleucylphenylalanine (fMLP) were inhibited by the antibiotic cerulenin, which inhibits fatty acid and cholesterol biosynthesis. The inhibition of O2- generation and Ca2+-mobilization required certain periods of incubation with cerulenin and both abilities of the cells were gradually lost following a similar time-course. In contrast, significant Ca2+-influx from the medium was observed in cerulenin-treated cells as well as untreated cells. The results suggest that an event which coincides with the Ca2+-mobilization and not Ca2+ per se is important for the induction of O2- generation in the fMLP-stimulated cells and that this step is blocked in cerulenin-treated cells. Phorbol myristate acetate or synthetic 1-oleoyl-2-acetylglycerol were able to bypass the block and induced O2- generation in cerulenin-treated cells.
Nakata
M
M
Institute of Medical Science, University of Tokyo, Japan.
Tomita
T
T
Iizuka
T
T
Kanegasaki
S
S
D000935:Antifungal Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002569:Cerulenin / Q000494:pharmacology*; D004075:Diglycerides / Q000494:pharmacology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects*; D012969:Sodium Fluoride / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000935:Antifungal Agents; D001427:Bacterial Toxins; D004075:Diglycerides; C025971:staphylococcal delta toxin; D013481:Superoxides; D002569:Cerulenin; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C038237:1-oleoyl-2-acetylglycerol; D012969:Sodium Fluoride; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen; D002118:Calcium