Nystatin stimulates prostaglandin E synthesis and formation of diacylglycerol in human monocytes.

The effect of the channel forming antibiotic nystatin on human monocytes was studied. Monocytes isolated from the peripheral blood (Mo), the monocytic cell line U937 and the promyelocytic cell line HL60 were used. Each cell type could be lysed with nystatin. The dose of nystatin required, however, was different for each cell line. In sublytic doses nystatin induced a rise of intracellular Ca2+, measured with the calcium indicator quin2. The rise of intracellular Ca2+ was followed by the release of prostaglandin E. By preincubation of the cells with quin2 the prostanoid synthesis could be inhibited suggesting that the increased Ca2+-levels could function as a signal. The prostanoid synthesis was also suppressed by inhibitors of the arachidonic acid pathway. Furthermore, nystatin induced an increase of diacylglycerol and a decrease of phosphatidylinositol. The generation of diacylglycerol, however, was not due to hydrolysis of the polyphosphoinositides because no increase of the second messenger inositol-1,4,5-triphosphate could be detected.