Inhibitory effect of amphotericin B on leukotriene B4 synthesis in human neutrophils in vitro.
Our objective was to determine the effect of amphotericin B on leukotriene (LT) A4 hydrolase in human neutrophil cytosol and to examine its effect on intact neutrophils in vitro. Cytosolic fractions were assayed for LTA4 hydrolase and 5-lipoxygenase activity in the presence or absence of amphotericin B. The IC50 of amphotericin B for LTA4 hydrolase activity was 0.72 microM. No inhibition of 5-lipoxygenase activity in the cytosolic fraction was detected. The IC50 of amphotericin B for leukotriene B4 synthesis in intact neutrophils was 0.43 microM. The 5-hydro(per) oxy-eicosatetraenoic acid (5-H(P)ETE) synthesis was diminished in intact cells by 66.8 [3.4]% (mean[SEM]) in the presence of 0.01 mM amphotericin B. Thus, amphotericin B inhibited the synthesis of LTB4 and 5-H(P)ETE in neutrophils in vitro. Differences between the results of studies on cytosol and on intact cells suggest that amphotericin B is involved in a complex interaction in the intact cell.
Shindo
K
K
The First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.
Fukumura
M
M
Ito
A
A
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004851:Epoxide Hydrolases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure
D000900:Anti-Bacterial Agents; D007975:Leukotriene B4; D000666:Amphotericin B; D001094:Arachidonate 5-Lipoxygenase; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase