POLYUNSATURATED FATTY-ACIDS REDUCE PYROGEN-INDUCED TISSUE FACTOR EXPRESSION IN HUMAN MONOCYTES

Endotoxin (LPS) and interleukin-1 beta (IL-1 beta) increased the expre ssion of tissue factor, a membrane-anchored glycoprotein that initiate s blood coagulation on the surface of cultured human umbilical vein en dothelial cells (HUVEC) and human monocyte/macrophages. On monocyte/ma crophages, oleic acid strongly inhibited LPS-induced tissue factor exp ression, a similar activity also being obtained with regard to the pyr ogenic effects of IL-1 beta. Other polyunsaturated fatty acids such as linoleic or linolenic acid also reduced tissue factor expression wher eas palmitic acid was ineffective. In contrast, these compounds showed no effect on LPS- or IL-1 beta-induced tissue factor expression in HU VEC when tested at the concentration of 10 mu M. These data therefore suggest that the well-recognized antithrombotic and antiatherogenic ef fect of polyunsaturated fatty acids may in part be mediated through an inhibition of tissue factor expression in monocyte/macrophages.