INHIBITORY EFFECT OF AMPHOTERICIN-B ON LEUKOTRIENE B-4 SYNTHESIS IN HUMAN NEUTROPHILS IN-VITRO

Our objective was to determine the effect of amphotericin B on leukotr iene (LT) A(4) hydrolase in human neutrophil cytosol and to examine it s effect on intact neutrophils in vitro. Cytosolic fractions were assa yed for LTA(4) hydrolase and 5-lipoxygenase activity in the presence o r absence of amphotericin B. The IC50 of amphotericin B for LTA(4) hyd rolase activity was 0.72 mu M. No inhibition of 5-lipoxygenase activit y in the cytosolic fraction was detected. The IC50 of amphotericin B f or leukotriene B-4 synthesis in intact neutrophils was 0.43 mu M. The 5-hydro(per)oxy-eicosatetraenoic acid (5-H(P)ETE) synthesis was dimini shed in intact cells by 66.8 [3.4]% (mean[SEM]) in the presence of 0.0 1 mM amphotericin B. Thus, amphotericin B inhibited the synthesis of L TB4 and 5-H(P)ETE in neutrophils in vitro. Differences between the res ults of studies on cytosol and on intact cells suggest that amphoteric in B is involved in a complex interaction in the intact cell.