Abstract
Our objective was to determine the effect of amphotericin B on leukotriene (LT) A 4 hydrolase in human neutrophil cytosol and to examine its effect on intact neutrophils in vitro. Cytosolic fractions were assayed for LTA 4 hydrolase and 5-lipoxygenase activity in the presence or absence of amphotericin B. The IC 50 of amphotericin B for LTA 4 hydrolase activity was 0.72 μM. No inhibition of 5-lipoxygenase activity in the cytosolic fraction was detected. The IC 50 of amphotericin B for leukotriene B 4 synthesis in intact neutrophils was 0.43 μM. 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 LTB 4 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.
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